annotation_CSV/PMC5173035.csv

anno_start	anno_end	anno_text	entity_type	sentence	section
0	43	Biochemical and structural characterization	experimental_method	Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori	TITLE
49	81	DNA N6-adenine methyltransferase	protein_type	Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori	TITLE
87	106	Helicobacter pylori	species	Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori	TITLE
0	20	DNA N6-methyladenine	ptm	DNA N6-methyladenine modification plays an important role in regulating a variety of biological functions in bacteria.	ABSTRACT
109	117	bacteria	taxonomy_domain	DNA N6-methyladenine modification plays an important role in regulating a variety of biological functions in bacteria.	ABSTRACT
59	75	N6-methyladenine	ptm	However, the mechanism of sequence-specific recognition in N6-methyladenine modification remains elusive.	ABSTRACT
0	9	M1.HpyAVI	protein	M1.HpyAVI, a DNA N6-adenine methyltransferase from Helicobacter pylori, shows more promiscuous substrate specificity than other enzymes.	ABSTRACT
13	45	DNA N6-adenine methyltransferase	protein_type	M1.HpyAVI, a DNA N6-adenine methyltransferase from Helicobacter pylori, shows more promiscuous substrate specificity than other enzymes.	ABSTRACT
51	70	Helicobacter pylori	species	M1.HpyAVI, a DNA N6-adenine methyltransferase from Helicobacter pylori, shows more promiscuous substrate specificity than other enzymes.	ABSTRACT
21	39	crystal structures	evidence	Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 Å and 3.1 Å, respectively.	ABSTRACT
43	56	cofactor-free	protein_state	Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 Å and 3.1 Å, respectively.	ABSTRACT
61	73	AdoMet-bound	protein_state	Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 Å and 3.1 Å, respectively.	ABSTRACT
74	84	structures	evidence	Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 Å and 3.1 Å, respectively.	ABSTRACT
22	31	M1.HpyAVI	protein	The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme.	ABSTRACT
56	78	AdoMet-dependent MTase	protein_type	The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme.	ABSTRACT
104	123	DNA binding regions	site	The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme.	ABSTRACT
168	174	MTases	protein_type	The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme.	ABSTRACT
0	25	Site-directed mutagenesis	experimental_method	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
58	61	D29	residue_name_number	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
66	70	E216	residue_name_number	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
123	129	methyl	chemical	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
169	172	P41	residue_name_number	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
187	202	highly flexible	protein_state	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
203	207	loop	structure_element	Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity.	ABSTRACT
66	98	DNA N6-adenine methyltransferase	protein_type	Taken together, our data revealed the structural basis underlying DNA N6-adenine methyltransferase substrate promiscuity.	ABSTRACT
0	15	DNA methylation	ptm	DNA methylation is a common form of modification on nucleic acids occurring in both prokaryotes and eukaryotes.	INTRO
84	95	prokaryotes	taxonomy_domain	DNA methylation is a common form of modification on nucleic acids occurring in both prokaryotes and eukaryotes.	INTRO
100	110	eukaryotes	taxonomy_domain	DNA methylation is a common form of modification on nucleic acids occurring in both prokaryotes and eukaryotes.	INTRO
60	63	DNA	chemical	Such a modification creates a signature motif recognized by DNA-interacting proteins and functions as a mechanism to regulate gene expression.	INTRO
0	15	DNA methylation	ptm	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
31	53	DNA methyltransferases	protein_type	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
55	61	MTases	protein_type	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
97	103	methyl	chemical	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
115	139	S-adenosyl-L- methionine	chemical	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
141	147	AdoMet	chemical	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
185	188	DNA	chemical	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
212	215	DNA	chemical	DNA methylation is mediated by DNA methyltransferases (MTases), which catalyze the transfer of a methyl group from S-adenosyl-L- methionine (AdoMet) to a given position of a particular DNA base within a specific DNA sequence.	INTRO
17	27	DNA MTases	protein_type	Three classes of DNA MTases have been identified to transfer a methyl group to different positions of DNA bases.	INTRO
63	69	methyl	chemical	Three classes of DNA MTases have been identified to transfer a methyl group to different positions of DNA bases.	INTRO
102	105	DNA	chemical	Three classes of DNA MTases have been identified to transfer a methyl group to different positions of DNA bases.	INTRO
0	18	C5-cytosine MTases	protein_type	C5-cytosine MTases, for example, methylate C5 of cytosine (m5C).	INTRO
49	57	cytosine	residue_name	C5-cytosine MTases, for example, methylate C5 of cytosine (m5C).	INTRO
59	62	m5C	ptm	C5-cytosine MTases, for example, methylate C5 of cytosine (m5C).	INTRO
3	13	eukaryotes	taxonomy_domain	In eukaryotes, m5C plays an important role in gene expression, chromatin organization, genome maintenance and parental imprinting, and is involved in a variety of human diseases including cancer.	INTRO
15	18	m5C	ptm	In eukaryotes, m5C plays an important role in gene expression, chromatin organization, genome maintenance and parental imprinting, and is involved in a variety of human diseases including cancer.	INTRO
163	168	human	species	In eukaryotes, m5C plays an important role in gene expression, chromatin organization, genome maintenance and parental imprinting, and is involved in a variety of human diseases including cancer.	INTRO
34	45	prokaryotic	taxonomy_domain	By contrast, the functions of the prokaryotic DNA cytosine MTase remain unknown.	INTRO
46	64	DNA cytosine MTase	protein_type	By contrast, the functions of the prokaryotic DNA cytosine MTase remain unknown.	INTRO
0	18	N4-cytosine MTases	protein_type	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
52	64	thermophilic	taxonomy_domain	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
68	78	mesophilic	taxonomy_domain	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
79	87	bacteria	taxonomy_domain	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
100	106	methyl	chemical	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
145	153	cytosine	residue_name	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
155	158	4mC	ptm	N4-cytosine MTases, which are frequently present in thermophilic or mesophilic bacteria, transfer a methyl group to the exocyclic amino group of cytosine (4mC).	INTRO
0	14	N4 methylation	ptm	N4 methylation seems to be primarily a component of bacterial immune system against invasion by foreign DNA, such as conjugative plasmids and bacteriophages.	INTRO
52	61	bacterial	taxonomy_domain	N4 methylation seems to be primarily a component of bacterial immune system against invasion by foreign DNA, such as conjugative plasmids and bacteriophages.	INTRO
104	107	DNA	chemical	N4 methylation seems to be primarily a component of bacterial immune system against invasion by foreign DNA, such as conjugative plasmids and bacteriophages.	INTRO
142	156	bacteriophages	taxonomy_domain	N4 methylation seems to be primarily a component of bacterial immune system against invasion by foreign DNA, such as conjugative plasmids and bacteriophages.	INTRO
17	34	N6-adenine MTases	protein_type	The third group, N6-adenine MTases methylate the exocyclic amino groups of adenine (6mA), which exists in prokaryotes as a signal for genome defense, DNA replication and repair, regulation of gene expression, control of transposition and host-pathogen interactions.	INTRO
75	82	adenine	residue_name	The third group, N6-adenine MTases methylate the exocyclic amino groups of adenine (6mA), which exists in prokaryotes as a signal for genome defense, DNA replication and repair, regulation of gene expression, control of transposition and host-pathogen interactions.	INTRO
84	87	6mA	ptm	The third group, N6-adenine MTases methylate the exocyclic amino groups of adenine (6mA), which exists in prokaryotes as a signal for genome defense, DNA replication and repair, regulation of gene expression, control of transposition and host-pathogen interactions.	INTRO
106	117	prokaryotes	taxonomy_domain	The third group, N6-adenine MTases methylate the exocyclic amino groups of adenine (6mA), which exists in prokaryotes as a signal for genome defense, DNA replication and repair, regulation of gene expression, control of transposition and host-pathogen interactions.	INTRO
150	153	DNA	chemical	The third group, N6-adenine MTases methylate the exocyclic amino groups of adenine (6mA), which exists in prokaryotes as a signal for genome defense, DNA replication and repair, regulation of gene expression, control of transposition and host-pathogen interactions.	INTRO
80	83	6mA	ptm	Recent studies utilizing new sequencing approaches have showed the existence of 6mA in several eukaryotic species.	INTRO
95	105	eukaryotic	taxonomy_domain	Recent studies utilizing new sequencing approaches have showed the existence of 6mA in several eukaryotic species.	INTRO
0	3	DNA	chemical	DNA 6mA modification is associated with important biological processes including nucleosome distribution close to the transcription start sites in Chlamydomonas, carrying heritable epigenetic information in C.elegans or controlling development of Drosophila.	INTRO
4	7	6mA	ptm	DNA 6mA modification is associated with important biological processes including nucleosome distribution close to the transcription start sites in Chlamydomonas, carrying heritable epigenetic information in C.elegans or controlling development of Drosophila.	INTRO
147	160	Chlamydomonas	taxonomy_domain	DNA 6mA modification is associated with important biological processes including nucleosome distribution close to the transcription start sites in Chlamydomonas, carrying heritable epigenetic information in C.elegans or controlling development of Drosophila.	INTRO
207	216	C.elegans	species	DNA 6mA modification is associated with important biological processes including nucleosome distribution close to the transcription start sites in Chlamydomonas, carrying heritable epigenetic information in C.elegans or controlling development of Drosophila.	INTRO
247	257	Drosophila	taxonomy_domain	DNA 6mA modification is associated with important biological processes including nucleosome distribution close to the transcription start sites in Chlamydomonas, carrying heritable epigenetic information in C.elegans or controlling development of Drosophila.	INTRO
23	34	methylation	ptm	All the three types of methylation exist in prokaryotes, and most DNA MTases are components of the restriction-modification (R-M) systems.	INTRO
44	55	prokaryotes	taxonomy_domain	All the three types of methylation exist in prokaryotes, and most DNA MTases are components of the restriction-modification (R-M) systems.	INTRO
66	76	DNA MTases	protein_type	All the three types of methylation exist in prokaryotes, and most DNA MTases are components of the restriction-modification (R-M) systems.	INTRO
17	41	restriction endonuclease	protein_type	“R” stands for a restriction endonuclease cleaving specific DNA sequences, while “M” symbolizes a modification methyltransferase rendering these sequences resistant to cleavage.	INTRO
60	63	DNA	chemical	“R” stands for a restriction endonuclease cleaving specific DNA sequences, while “M” symbolizes a modification methyltransferase rendering these sequences resistant to cleavage.	INTRO
98	128	modification methyltransferase	protein_type	“R” stands for a restriction endonuclease cleaving specific DNA sequences, while “M” symbolizes a modification methyltransferase rendering these sequences resistant to cleavage.	INTRO
79	87	bacteria	taxonomy_domain	The cooperation of these two enzymes provides a defensive mechanism to protect bacteria from infection by bacteriophages.	INTRO
106	120	bacteriophages	taxonomy_domain	The cooperation of these two enzymes provides a defensive mechanism to protect bacteria from infection by bacteriophages.	INTRO
99	102	DNA	chemical	The R-M systems are classified into three types based on specific structural features, position of DNA cleavage and cofactor requirements.	INTRO
24	65	DNA adenine or cytosine methyltransferase	protein_type	In types I and III, the DNA adenine or cytosine methyltransferase is part of a multi-subunit enzyme that catalyzes both restriction and modification.	INTRO
68	92	restriction endonuclease	protein_type	By contrast, two separate enzymes exist in type II systems, where a restriction endonuclease and a DNA adenine or cytosine methyltransferase recognize the same targets.	INTRO
99	140	DNA adenine or cytosine methyltransferase	protein_type	By contrast, two separate enzymes exist in type II systems, where a restriction endonuclease and a DNA adenine or cytosine methyltransferase recognize the same targets.	INTRO
21	30	bacterial	taxonomy_domain	To date, a number of bacterial DNA MTases have been structurally characterized, covering enzymes from all the three classes.	INTRO
31	41	DNA MTases	protein_type	To date, a number of bacterial DNA MTases have been structurally characterized, covering enzymes from all the three classes.	INTRO
52	78	structurally characterized	experimental_method	To date, a number of bacterial DNA MTases have been structurally characterized, covering enzymes from all the three classes.	INTRO
10	16	MTases	protein_type	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
120	129	conserved	protein_state	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
137	153	catalytic domain	structure_element	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
168	179	active site	site	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
184	190	methyl	chemical	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
215	221	AdoMet	chemical	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
245	276	target (DNA)-recognition domain	structure_element	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
278	281	TRD	structure_element	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
343	346	DNA	chemical	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
387	390	DNA	chemical	All these MTases exhibit high similarity in their overall architectures, which are generally folded into two domains: a conserved larger catalytic domain comprising an active site for methyl transfer and a site for AdoMet-binding, and a smaller target (DNA)-recognition domain (TRD) containing variable regions implicated in sequence-specific DNA recognition and the infiltration of the DNA to flip the target base.	INTRO
0	9	Conserved	protein_state	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
63	73	structures	evidence	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
97	100	I-X	structure_element	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
105	120	cytosine MTases	protein_type	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
138	144	I-VIII	structure_element	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
149	150	X	structure_element	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
155	169	adenine MTases	protein_type	Conserved amino acid motifs have been identified from reported structures, including ten motifs (I-X) in cytosine MTases and nine motifs (I-VIII and X) in adenine MTases, all of which are arranged in an almost constant order.	INTRO
45	54	conserved	protein_state	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
64	86	exocyclic amino MTases	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
126	127	α	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
129	130	β	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
132	133	γ	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
135	136	ζ	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
138	139	δ	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
144	145	ε	protein_type	According to the linear arrangement of three conserved domains, exocyclic amino MTases are subdivided into six groups (namely α, β, γ, ζ, δ and ε).	INTRO
0	33	N6-adenine and N4-cytosine MTases	protein_type	N6-adenine and N4-cytosine MTases, in particular, are closely related by sharing common structural features.	RESULTS
0	33	N6-adenine and N4-cytosine MTases	protein_type	N6-adenine and N4-cytosine MTases, in particular, are closely related by sharing common structural features.	RESULTS
42	51	bacterial	taxonomy_domain	Despite the considerable similarity among bacterial MTases, some differences were observed among the enzymes from various species.	INTRO
52	58	MTases	protein_type	Despite the considerable similarity among bacterial MTases, some differences were observed among the enzymes from various species.	INTRO
39	45	MTases	protein_type	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
57	73	catalytic domain	structure_element	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
107	124	C-terminal domain	structure_element	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
128	134	M.TaqI	protein	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
156	164	M.MboIIA	protein	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
169	175	M.RsrI	protein	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
181	193	helix bundle	structure_element	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
197	203	EcoDam	protein	For example, the structural regions of MTases beyond the catalytic domain are rather variable, such as the C-terminal domain of M.TaqI, the extended arm of M.MboIIA and M.RsrI, the helix bundle of EcoDam, and so on.	INTRO
0	15	DNA methylation	ptm	DNA methylation is thought to influence bacterial virulence.	INTRO
40	49	bacterial	taxonomy_domain	DNA methylation is thought to influence bacterial virulence.	INTRO
0	29	DNA adenine methyltransferase	protein_type	DNA adenine methyltransferase has been shown to play a crucial role in colonization of deep tissue sites in Salmonella typhimurium and Aeromonas hydrophila.	INTRO
108	130	Salmonella typhimurium	species	DNA adenine methyltransferase has been shown to play a crucial role in colonization of deep tissue sites in Salmonella typhimurium and Aeromonas hydrophila.	INTRO
135	155	Aeromonas hydrophila	species	DNA adenine methyltransferase has been shown to play a crucial role in colonization of deep tissue sites in Salmonella typhimurium and Aeromonas hydrophila.	INTRO
13	36	DNA adenine methylation	ptm	Importantly, DNA adenine methylation is a global regulator of genes expressed during infection and inhibitors of DNA adenine methylation are likely to have a broad antimicrobial action.	INTRO
113	136	DNA adenine methylation	ptm	Importantly, DNA adenine methylation is a global regulator of genes expressed during infection and inhibitors of DNA adenine methylation are likely to have a broad antimicrobial action.	INTRO
0	3	Dam	protein_type	Dam was considered a promising target for antimicrobial drug development.	INTRO
0	19	Helicobacter pylori	species	Helicobacter pylori is a Gram-negative bacterium that persistently colonizes in human stomach worldwide.	INTRO
25	48	Gram-negative bacterium	taxonomy_domain	Helicobacter pylori is a Gram-negative bacterium that persistently colonizes in human stomach worldwide.	INTRO
80	85	human	species	Helicobacter pylori is a Gram-negative bacterium that persistently colonizes in human stomach worldwide.	INTRO
0	9	H. pylori	species	H. pylori is involved in 90% of all gastric malignancies, infecting nearly 50% of the world's population and is the most crucial etiologic agent for gastric adenocarcinoma.	INTRO
0	9	H. pylori	species	H. pylori strains possess a few R-M systems like other bacteria to function as defensive systems.	INTRO
55	63	bacteria	taxonomy_domain	H. pylori strains possess a few R-M systems like other bacteria to function as defensive systems.	INTRO
0	15	H. pylori 26695	species	H. pylori 26695, for example, has 23 R-M systems.	INTRO
0	18	Methyltransferases	protein_type	Methyltransferases were suggested to be involved in H. pylori pathogenicity.	INTRO
52	61	H. pylori	species	Methyltransferases were suggested to be involved in H. pylori pathogenicity.	INTRO
0	9	M1.HpyAVI	protein	M1.HpyAVI is a DNA adenine MTase that belongs to the type II R-M system.	INTRO
15	32	DNA adenine MTase	protein_type	M1.HpyAVI is a DNA adenine MTase that belongs to the type II R-M system.	INTRO
25	35	DNA MTases	protein_type	This system contains two DNA MTases named M1.HpyAVI and M2.HpyAVI, and a putative restriction enzyme.	INTRO
42	51	M1.HpyAVI	protein	This system contains two DNA MTases named M1.HpyAVI and M2.HpyAVI, and a putative restriction enzyme.	INTRO
56	65	M2.HpyAVI	protein	This system contains two DNA MTases named M1.HpyAVI and M2.HpyAVI, and a putative restriction enzyme.	INTRO
82	100	restriction enzyme	protein_type	This system contains two DNA MTases named M1.HpyAVI and M2.HpyAVI, and a putative restriction enzyme.	INTRO
0	9	M1.HpyAVI	protein	M1.HpyAVI encoded by ORF hp0050 is an N6-adenine methyltransferase belonging to the β-class MTase.	INTRO
25	31	hp0050	gene	M1.HpyAVI encoded by ORF hp0050 is an N6-adenine methyltransferase belonging to the β-class MTase.	INTRO
38	66	N6-adenine methyltransferase	protein_type	M1.HpyAVI encoded by ORF hp0050 is an N6-adenine methyltransferase belonging to the β-class MTase.	INTRO
84	97	β-class MTase	protein_type	M1.HpyAVI encoded by ORF hp0050 is an N6-adenine methyltransferase belonging to the β-class MTase.	INTRO
74	85	5′-GAGG-3′,	chemical	It has been reported recently that this enzyme recognizes the sequence of 5′-GAGG-3′, 5′-GGAG-3′ or 5′-GAAG-3′ and methylates adenines in these sequences.	INTRO
86	96	5′-GGAG-3′	chemical	It has been reported recently that this enzyme recognizes the sequence of 5′-GAGG-3′, 5′-GGAG-3′ or 5′-GAAG-3′ and methylates adenines in these sequences.	INTRO
100	110	5′-GAAG-3′	chemical	It has been reported recently that this enzyme recognizes the sequence of 5′-GAGG-3′, 5′-GGAG-3′ or 5′-GAAG-3′ and methylates adenines in these sequences.	INTRO
126	134	adenines	residue_name	It has been reported recently that this enzyme recognizes the sequence of 5′-GAGG-3′, 5′-GGAG-3′ or 5′-GAAG-3′ and methylates adenines in these sequences.	INTRO
11	22	methylation	ptm	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
39	47	adenines	residue_name	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
102	119	N6-adenine MTases	protein_type	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
125	136	methylation	ptm	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
149	159	5′-GAAG-3′	chemical	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
192	201	M1.HpyAVI	protein	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
252	260	H.pylori	species	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
293	303	5′-GAGG-3′	chemical	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
449	458	structure	evidence	Given that methylation of two adjacent adenines on the same strand have never been observed for other N6-adenine MTases, the methylation activity on 5′-GAAG-3′ seems to be a unique feature of M1.HpyAVI, compared with the homologs from other strains of H.pylori which is able to methylate only 5′-GAGG-3′. The structural basis and the catalytic mechanism underlying such a distinct activity are not well understood due to the lack of an available 3D structure of this enzyme.	INTRO
20	37	crystal structure	evidence	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
41	50	M1.HpyAVI	protein	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
56	71	H. pylori 26695	species	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
103	119	N6-adenine MTase	protein_type	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
120	129	structure	evidence	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
133	142	H. pylori	species	Here, we report the crystal structure of M1.HpyAVI from H. pylori 26695, which is the first determined N6-adenine MTase structure in H. pylori.	INTRO
4	13	structure	evidence	The structure reveals a similar architecture as the canonical fold of homologous proteins, but displays several differences in the loop regions and TRD.	INTRO
131	135	loop	structure_element	The structure reveals a similar architecture as the canonical fold of homologous proteins, but displays several differences in the loop regions and TRD.	INTRO
148	151	TRD	structure_element	The structure reveals a similar architecture as the canonical fold of homologous proteins, but displays several differences in the loop regions and TRD.	INTRO
9	44	structural and biochemical analyses	experimental_method	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
69	78	conserved	protein_state	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
92	95	D29	residue_name_number	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
103	117	catalytic site	site	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
122	126	E216	residue_name_number	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
197	214	methyltransferase	protein_type	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
227	236	M1.HpyAVI	protein	Based on structural and biochemical analyses, we then identified two conserved amino acids, D29 at the catalytic site and E216 close to the C-terminus, as crucial residues for cofactor binding and methyltransferase activity of M1.HpyAVI.	INTRO
15	28	non-conserved	protein_state	In addition, a non-conserved amino acid, P41, seems to play a key role in substrate recognition.	INTRO
41	44	P41	residue_name_number	In addition, a non-conserved amino acid, P41, seems to play a key role in substrate recognition.	INTRO
8	17	structure	evidence	Overall structure	RESULTS
12	23	full-length	protein_state	Recombinant full-length M1.HpyAVI was produced as a soluble protein in Escherichia coli, but was quite unstable and tended to aggregate in low salt environment.	RESULTS
24	33	M1.HpyAVI	protein	Recombinant full-length M1.HpyAVI was produced as a soluble protein in Escherichia coli, but was quite unstable and tended to aggregate in low salt environment.	RESULTS
71	87	Escherichia coli	species	Recombinant full-length M1.HpyAVI was produced as a soluble protein in Escherichia coli, but was quite unstable and tended to aggregate in low salt environment.	RESULTS
92	107	sodium chloride	chemical	The protein, however, remained fully soluble in a buffer containing higher concentration of sodium chloride (>300 mM), which prompted that M1.HpyAVI is likely a halophilic protein.	RESULTS
139	148	M1.HpyAVI	protein	The protein, however, remained fully soluble in a buffer containing higher concentration of sodium chloride (>300 mM), which prompted that M1.HpyAVI is likely a halophilic protein.	RESULTS
161	171	halophilic	protein_state	The protein, however, remained fully soluble in a buffer containing higher concentration of sodium chloride (>300 mM), which prompted that M1.HpyAVI is likely a halophilic protein.	RESULTS
4	17	cofactor-free	protein_state	The cofactor-free and AdoMet-bound proteins were crystallized at different conditions.	RESULTS
22	34	AdoMet-bound	protein_state	The cofactor-free and AdoMet-bound proteins were crystallized at different conditions.	RESULTS
49	61	crystallized	experimental_method	The cofactor-free and AdoMet-bound proteins were crystallized at different conditions.	RESULTS
5	15	structures	evidence	Both structures were determined by means of molecular replacement, and refined to 3.0 Å and 3.1 Å, respectively.	RESULTS
44	65	molecular replacement	experimental_method	Both structures were determined by means of molecular replacement, and refined to 3.0 Å and 3.1 Å, respectively.	RESULTS
14	35	X-ray data collection	experimental_method	Statistics of X-ray data collection and structure refinement were summarized in Table 1.	RESULTS
40	60	structure refinement	experimental_method	Statistics of X-ray data collection and structure refinement were summarized in Table 1.	RESULTS
20	51	structure refinement statistics	evidence	Data collection and structure refinement statistics of M1.HpyAVI	TABLE
55	64	M1.HpyAVI	protein	Data collection and structure refinement statistics of M1.HpyAVI	TABLE
1	10	M1.HpyAVI	protein	"	M1.HpyAVI	M1.HpyAVI-AdoMet complex	 	Data collection			 	Wavelength (Å)	1.0000	0.97772	 	Space group	P43212	P65	 	Unit-cell parameters (Å, ˚)	a = b = 69.73, c = 532.75α = β = γ = 90	a = b = 135.60, c = 265.15α = β = 90, γ = 120	 	Resolution range (Å) a	49.09-3.00 (3.09-3.00)	48.91-3.10 (3.18-3.10)	 	Unique reflections a	27243	49833	 	Multiplicity a	3.7 (3.8)	5.6 (4.0)	 	Completeness (%)a	98.7 (98.9)	99.7 (97.8)	 	Mean I/δ (I) a	12.1 (3.4)	14.0 (1.9)	 	Solvent content (%)	58.67	61.96	 	Rmergea	0.073 (0.378)	0.106 (0.769)	 	Structure refinement			 	Rwork	0.251	0.221	 	Rfree	0.308	0.276	 	R.m.s.d., bond lengths (Å)	0.007	0.007	 	R.m.s.d., bond angles (˚)	1.408	1.651	 	Ramachandran plot			 	Favoured region (%)	89.44	91.44	 	Allowed region (%)	9.58	7.11	 	Outliers (%)	0.99	1.45	 	"	TABLE
11	27	M1.HpyAVI-AdoMet	complex_assembly	"	M1.HpyAVI	M1.HpyAVI-AdoMet complex	 	Data collection			 	Wavelength (Å)	1.0000	0.97772	 	Space group	P43212	P65	 	Unit-cell parameters (Å, ˚)	a = b = 69.73, c = 532.75α = β = γ = 90	a = b = 135.60, c = 265.15α = β = 90, γ = 120	 	Resolution range (Å) a	49.09-3.00 (3.09-3.00)	48.91-3.10 (3.18-3.10)	 	Unique reflections a	27243	49833	 	Multiplicity a	3.7 (3.8)	5.6 (4.0)	 	Completeness (%)a	98.7 (98.9)	99.7 (97.8)	 	Mean I/δ (I) a	12.1 (3.4)	14.0 (1.9)	 	Solvent content (%)	58.67	61.96	 	Rmergea	0.073 (0.378)	0.106 (0.769)	 	Structure refinement			 	Rwork	0.251	0.221	 	Rfree	0.308	0.276	 	R.m.s.d., bond lengths (Å)	0.007	0.007	 	R.m.s.d., bond angles (˚)	1.408	1.651	 	Ramachandran plot			 	Favoured region (%)	89.44	91.44	 	Allowed region (%)	9.58	7.11	 	Outliers (%)	0.99	1.45	 	"	TABLE
594	601	R.m.s.d	evidence	"	M1.HpyAVI	M1.HpyAVI-AdoMet complex	 	Data collection			 	Wavelength (Å)	1.0000	0.97772	 	Space group	P43212	P65	 	Unit-cell parameters (Å, ˚)	a = b = 69.73, c = 532.75α = β = γ = 90	a = b = 135.60, c = 265.15α = β = 90, γ = 120	 	Resolution range (Å) a	49.09-3.00 (3.09-3.00)	48.91-3.10 (3.18-3.10)	 	Unique reflections a	27243	49833	 	Multiplicity a	3.7 (3.8)	5.6 (4.0)	 	Completeness (%)a	98.7 (98.9)	99.7 (97.8)	 	Mean I/δ (I) a	12.1 (3.4)	14.0 (1.9)	 	Solvent content (%)	58.67	61.96	 	Rmergea	0.073 (0.378)	0.106 (0.769)	 	Structure refinement			 	Rwork	0.251	0.221	 	Rfree	0.308	0.276	 	R.m.s.d., bond lengths (Å)	0.007	0.007	 	R.m.s.d., bond angles (˚)	1.408	1.651	 	Ramachandran plot			 	Favoured region (%)	89.44	91.44	 	Allowed region (%)	9.58	7.11	 	Outliers (%)	0.99	1.45	 	"	TABLE
635	642	R.m.s.d	evidence	"	M1.HpyAVI	M1.HpyAVI-AdoMet complex	 	Data collection			 	Wavelength (Å)	1.0000	0.97772	 	Space group	P43212	P65	 	Unit-cell parameters (Å, ˚)	a = b = 69.73, c = 532.75α = β = γ = 90	a = b = 135.60, c = 265.15α = β = 90, γ = 120	 	Resolution range (Å) a	49.09-3.00 (3.09-3.00)	48.91-3.10 (3.18-3.10)	 	Unique reflections a	27243	49833	 	Multiplicity a	3.7 (3.8)	5.6 (4.0)	 	Completeness (%)a	98.7 (98.9)	99.7 (97.8)	 	Mean I/δ (I) a	12.1 (3.4)	14.0 (1.9)	 	Solvent content (%)	58.67	61.96	 	Rmergea	0.073 (0.378)	0.106 (0.769)	 	Structure refinement			 	Rwork	0.251	0.221	 	Rfree	0.308	0.276	 	R.m.s.d., bond lengths (Å)	0.007	0.007	 	R.m.s.d., bond angles (˚)	1.408	1.651	 	Ramachandran plot			 	Favoured region (%)	89.44	91.44	 	Allowed region (%)	9.58	7.11	 	Outliers (%)	0.99	1.45	 	"	TABLE
23	31	monomers	oligomeric_state	Four and eight protein monomers resided in the asymmetric units of the two crystal structures.	RESULTS
75	93	crystal structures	evidence	Four and eight protein monomers resided in the asymmetric units of the two crystal structures.	RESULTS
48	53	loops	structure_element	Some amino acids, particularly those within two loops (residues 32-61 and 152-172) in both structures, were poorly defined in electron density and had to be omitted from the refined models.	RESULTS
64	69	32-61	residue_range	Some amino acids, particularly those within two loops (residues 32-61 and 152-172) in both structures, were poorly defined in electron density and had to be omitted from the refined models.	RESULTS
74	81	152-172	residue_range	Some amino acids, particularly those within two loops (residues 32-61 and 152-172) in both structures, were poorly defined in electron density and had to be omitted from the refined models.	RESULTS
91	101	structures	evidence	Some amino acids, particularly those within two loops (residues 32-61 and 152-172) in both structures, were poorly defined in electron density and had to be omitted from the refined models.	RESULTS
126	142	electron density	evidence	Some amino acids, particularly those within two loops (residues 32-61 and 152-172) in both structures, were poorly defined in electron density and had to be omitted from the refined models.	RESULTS
8	18	structures	evidence	The two structures are very similar to each other (Figure 1) and could be well overlaid with an RMSD of 0.76 Å on 191 Cα atoms.	RESULTS
96	100	RMSD	evidence	The two structures are very similar to each other (Figure 1) and could be well overlaid with an RMSD of 0.76 Å on 191 Cα atoms.	RESULTS
28	37	M1.HpyAVI	protein	The overall architecture of M1.HpyAVI revealed in these structures resembles the AdoMet-dependent MTase fold in which a twisted seven-stranded β-sheet flanked by six α-helices forms the structural core.	RESULTS
56	66	structures	evidence	The overall architecture of M1.HpyAVI revealed in these structures resembles the AdoMet-dependent MTase fold in which a twisted seven-stranded β-sheet flanked by six α-helices forms the structural core.	RESULTS
81	103	AdoMet-dependent MTase	protein_type	The overall architecture of M1.HpyAVI revealed in these structures resembles the AdoMet-dependent MTase fold in which a twisted seven-stranded β-sheet flanked by six α-helices forms the structural core.	RESULTS
143	150	β-sheet	structure_element	The overall architecture of M1.HpyAVI revealed in these structures resembles the AdoMet-dependent MTase fold in which a twisted seven-stranded β-sheet flanked by six α-helices forms the structural core.	RESULTS
166	175	α-helices	structure_element	The overall architecture of M1.HpyAVI revealed in these structures resembles the AdoMet-dependent MTase fold in which a twisted seven-stranded β-sheet flanked by six α-helices forms the structural core.	RESULTS
18	28	structures	evidence	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
53	59	MTases	protein_type	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
67	74	helices	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
76	78	αA	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
80	82	αB	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
87	89	αZ	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
130	137	β-sheet	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
161	163	αD	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
165	167	αE	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
172	174	αC	structure_element	Like the reported structures of the larger domain of MTases, three helices (αA, αB and αZ) are located at one face of the central β-sheet, while the other three αD, αE and αC sit at the other side.	RESULTS
10	19	conserved	protein_state	All these conserved structural motifs form a typical α/β Rossmann fold.	RESULTS
53	70	α/β Rossmann fold	structure_element	All these conserved structural motifs form a typical α/β Rossmann fold.	RESULTS
4	19	catalytic motif	structure_element	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
20	24	DPPY	structure_element	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
35	39	loop	structure_element	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
51	53	αD	structure_element	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
58	60	β4	structure_element	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
79	85	AdoMet	chemical	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
109	115	cavity	site	The catalytic motif DPPY lies in a loop connecting αD and β4, and the cofactor AdoMet binds in a neighboring cavity.	RESULTS
4	8	loop	structure_element	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
19	26	136-166	residue_range	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
44	46	β7	structure_element	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
51	53	αZ	structure_element	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
71	85	highly diverse	protein_state	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
102	108	MTases	protein_type	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
136	139	DNA	chemical	The loop (residues 136-166) located between β7 and αZ corresponds to a highly diverse region in other MTases that is involved in target DNA recognition.	RESULTS
4	16	hairpin loop	structure_element	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
27	34	101-133	residue_range	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
45	47	β6	structure_element	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
52	54	β7	structure_element	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
82	85	DNA	chemical	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
93	105	minor groove	structure_element	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
160	168	M.MboIIA	protein	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
170	176	M.RsrI	protein	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
181	188	M.pvuII	protein	The hairpin loop (residues 101-133) bridging β6 and β7, which is proposed to bind DNA in the minor groove, displays a similar conformation as those observed in M.MboIIA, M.RsrI and M.pvuII.	RESULTS
4	11	missing	protein_state	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
12	16	loop	structure_element	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
27	32	33-58	residue_range	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
41	50	structure	evidence	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
54	63	M1.HpyAVI	protein	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
79	85	loop I	structure_element	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
89	95	M.TaqI	protein	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
127	136	structure	evidence	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
137	148	without DNA	protein_state	The missing loop (residues 33-58) in the structure of M1.HpyAVI corresponds to loop I in M.TaqI, which was also invisible in a structure without DNA.	RESULTS
5	9	loop	structure_element	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
24	36	well ordered	protein_state	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
43	71	M.TaqI-DNA complex structure	evidence	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
112	127	DNA methylation	ptm	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
155	162	adenine	residue_name	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
188	191	DNA	chemical	This loop, however, was well ordered in an M.TaqI-DNA complex structure and was shown to play a crucial role in DNA methylation by contacting the flipping adenine and recognizing specific DNA sequence.	RESULTS
8	17	structure	evidence	Overall structure of M1.HpyAVI	FIG
21	30	M1.HpyAVI	protein	Overall structure of M1.HpyAVI	FIG
3	7	Free	protein_state	A. Free form B. AdoMet-bound form.	FIG
16	28	AdoMet-bound	protein_state	A. Free form B. AdoMet-bound form.	FIG
18	27	M1.HpyAVI	protein	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
42	64	AdoMet-dependent MTase	protein_type	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
95	102	β-sheet	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
118	127	α-helices	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
129	131	αA	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
133	135	αB	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
137	139	αZ	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
156	158	αD	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
160	162	αE	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
164	166	αC	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
199	205	AdoMet	chemical	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
209	217	bound in	protein_state	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
220	226	cavity	site	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
236	245	conserved	protein_state	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
268	272	DPPY	structure_element	Ribbon diagram of M1.HpyAVI resembles an “AdoMet-dependent MTase fold”, a mixed seven-stranded β-sheet flanked by six α-helices, αA, αB, αZ on one side and αD, αE, αC on the other side, the cofactor AdoMet is bound in a cavity near the conserved enzyme activity motif DPPY.	FIG
4	13	α-helices	structure_element	The α-helices and β-strands are labelled and numbered according to the commonly numbering rule for the known MTases.	FIG
18	27	β-strands	structure_element	The α-helices and β-strands are labelled and numbered according to the commonly numbering rule for the known MTases.	FIG
109	115	MTases	protein_type	The α-helices and β-strands are labelled and numbered according to the commonly numbering rule for the known MTases.	FIG
4	10	AdoMet	chemical	The AdoMet molecule is shown in green.	FIG
0	7	Dimeric	oligomeric_state	Dimeric state of M1.HpyAVI in crystal and solution	RESULTS
17	26	M1.HpyAVI	protein	Dimeric state of M1.HpyAVI in crystal and solution	RESULTS
30	37	crystal	evidence	Dimeric state of M1.HpyAVI in crystal and solution	RESULTS
42	50	solution	experimental_method	Dimeric state of M1.HpyAVI in crystal and solution	RESULTS
34	44	DNA MTases	protein_type	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
51	58	M.BamHI	protein	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
63	70	M.EcoRI	protein	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
81	88	monomer	oligomeric_state	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
136	139	DNA	chemical	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
164	169	MTase	protein_type	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
173	187	hemimethylated	protein_state	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
222	233	methylation	ptm	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
261	277	fully methylated	protein_state	Previous studies showed that some DNA MTases, e.g. M.BamHI and M.EcoRI, exist as monomer in solution, in agreement with the fact that a DNA substrate for a typical MTase is hemimethylated and therefore needs only a single methylation event to convert it into a fully methylated state.	RESULTS
21	28	dimeric	oligomeric_state	Increasing number of dimeric DNA MTases, however, has been identified from later studies.	RESULTS
29	39	DNA MTases	protein_type	Increasing number of dimeric DNA MTases, however, has been identified from later studies.	RESULTS
14	21	M.DpnII	protein	For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution.	RESULTS
23	29	M.RsrI	protein	For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution.	RESULTS
31	37	M.KpnI	protein	For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution.	RESULTS
43	51	M.MboIIA	protein	For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution.	RESULTS
71	77	dimers	oligomeric_state	For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution.	RESULTS
21	27	MTases	protein_type	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
38	46	M.MboIIA	protein	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
48	54	M.RsrI	protein	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
59	66	TTH0409	protein	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
91	97	dimers	oligomeric_state	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
101	119	crystal structures	evidence	In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures.	RESULTS
18	28	DNA MTases	protein_type	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
37	44	M.CcrMI	protein	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
53	79	Bacillus amyloliquefaciens	species	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
80	85	MTase	protein_type	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
102	107	dimer	oligomeric_state	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
113	120	monomer	oligomeric_state	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
126	129	DNA	chemical	Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding.	RESULTS
42	51	conserved	protein_state	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
61	70	M1.HpyAVI	protein	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
86	96	β-subgroup	protein_type	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
109	118	conserved	protein_state	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
125	180	NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A	structure_element	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
208	230	dimerization interface	site	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
234	252	crystal structures	evidence	According to the arrangement of the three conserved domains, M1.HpyAVI belongs to the β-subgroup, in which a conserved motif NXXTX9−11AXRXFSXXHX4WX6−9 YXFXLX3RX9−26NPX1−6NVWX29−34A has been identified at the dimerization interface in crystal structures.	RESULTS
8	17	conserved	protein_state	Most of conserved amino acids within that motif are present in the sequence of M1.HpyAVI (Figure 2A), implying dimerization of this protein.	RESULTS
79	88	M1.HpyAVI	protein	Most of conserved amino acids within that motif are present in the sequence of M1.HpyAVI (Figure 2A), implying dimerization of this protein.	RESULTS
111	123	dimerization	oligomeric_state	Most of conserved amino acids within that motif are present in the sequence of M1.HpyAVI (Figure 2A), implying dimerization of this protein.	RESULTS
16	21	dimer	oligomeric_state	In agreement, a dimer of M1.HpyAVI was observed in our crystal structures with the two monomers related by a two-fold axis (Figure 2B and 2C).	RESULTS
25	34	M1.HpyAVI	protein	In agreement, a dimer of M1.HpyAVI was observed in our crystal structures with the two monomers related by a two-fold axis (Figure 2B and 2C).	RESULTS
55	73	crystal structures	evidence	In agreement, a dimer of M1.HpyAVI was observed in our crystal structures with the two monomers related by a two-fold axis (Figure 2B and 2C).	RESULTS
87	95	monomers	oligomeric_state	In agreement, a dimer of M1.HpyAVI was observed in our crystal structures with the two monomers related by a two-fold axis (Figure 2B and 2C).	RESULTS
38	55	dimeric interface	site	An area of ~1900 Å2 was buried at the dimeric interface, taking up ca 17% of the total area.	RESULTS
4	11	dimeric	oligomeric_state	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
51	65	hydrogen bonds	bond_interaction	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
70	82	salt bridges	bond_interaction	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
105	108	R86	residue_name_number	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
110	113	D93	residue_name_number	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
118	121	E96	residue_name_number	The dimeric architecture was greatly stabilized by hydrogen bonds and salt bridges formed among residues R86, D93 and E96.	RESULTS
31	36	dimer	oligomeric_state	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
37	46	structure	evidence	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
50	59	M1.HpyAVI	protein	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
76	90	β-class MTases	protein_type	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
92	101	M1.MboIIA	protein	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
103	109	M.RsrI	protein	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
114	122	TTHA0409	protein	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
143	152	M1.HpyAVI	protein	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
153	158	dimer	oligomeric_state	In addition, comparison of the dimer structure of M1.HpyAVI with some other β-class MTases (M1.MboIIA, M.RsrI and TTHA0409) suggested that the M1.HpyAVI dimer organized in a similar form as others (Figure S3).	RESULTS
0	9	M1.HpyAVI	protein	M1.HpyAVI exists as dimer in crystal and solution	FIG
20	25	dimer	oligomeric_state	M1.HpyAVI exists as dimer in crystal and solution	FIG
29	36	crystal	evidence	M1.HpyAVI exists as dimer in crystal and solution	FIG
5	14	conserved	protein_state	A. A conserved interface area of β-class MTases is defined in M1.HpyAVI.	FIG
15	29	interface area	site	A. A conserved interface area of β-class MTases is defined in M1.HpyAVI.	FIG
33	47	β-class MTases	protein_type	A. A conserved interface area of β-class MTases is defined in M1.HpyAVI.	FIG
62	71	M1.HpyAVI	protein	A. A conserved interface area of β-class MTases is defined in M1.HpyAVI.	FIG
48	60	Dimerization	oligomeric_state	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
64	68	free	protein_state	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
74	83	M1.HpyAVI	protein	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
91	105	cofactor-bound	protein_state	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
106	115	M1.HpyAVI	protein	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
127	135	monomers	oligomeric_state	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
166	172	AdoMet	chemical	Residues that involved are signed in red color; Dimerization of free-form M1.HpyAVI B. and cofactor-bound M1.HpyAVI C. The two monomers are marked in green and blue, AdoMet molecules are marked in magenta.	FIG
3	26	Gel-filtration analysis	experimental_method	D. Gel-filtration analysis revealed that M1.HpyAVI exist as a dimer in solution.	FIG
41	50	M1.HpyAVI	protein	D. Gel-filtration analysis revealed that M1.HpyAVI exist as a dimer in solution.	FIG
62	67	dimer	oligomeric_state	D. Gel-filtration analysis revealed that M1.HpyAVI exist as a dimer in solution.	FIG
0	4	FPLC	experimental_method	FPLC system coupled to a Superdex 75 10/300 column.	FIG
0	16	Elution profiles	evidence	Elution profiles at 280 nm (blue) and 260 nm (red) are: different concentration (0.05, 0.1, 0.2, 0.5 mg/ml) of M1.HpyAVI protein.	FIG
111	120	M1.HpyAVI	protein	Elution profiles at 280 nm (blue) and 260 nm (red) are: different concentration (0.05, 0.1, 0.2, 0.5 mg/ml) of M1.HpyAVI protein.	FIG
32	41	M1.HpyAVI	protein	To probe the oligomeric form of M1.HpyAVI in solution, different concentrations of purified enzyme was loaded onto a Superdex 75 10/300 column.	RESULTS
94	101	dimeric	oligomeric_state	The protein was eluted at ~10 ml regardless of the protein concentrations, corresponding to a dimeric molecular mass of 54 kDa (Figure 2D).	RESULTS
102	116	molecular mass	evidence	The protein was eluted at ~10 ml regardless of the protein concentrations, corresponding to a dimeric molecular mass of 54 kDa (Figure 2D).	RESULTS
32	41	M1.HpyAVI	protein	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
50	55	dimer	oligomeric_state	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
64	71	crystal	evidence	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
94	108	β-class MTases	protein_type	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
170	194	dynamic light scattering	experimental_method	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
196	199	DLS	experimental_method	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
217	246	gel-filtration chromatography	experimental_method	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
264	273	M1.HpyAVI	protein	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
286	295	monomeric	oligomeric_state	Our results clearly showed that M1.HpyAVI forms a dimer in both crystal and solution as other β-class MTases, which however disagrees with a previous investigation using dynamic light scattering (DLS) measurement and gel-filtration chromatography, suggesting that M1.HpyAVI is taking a monomeric state in solution.	RESULTS
55	63	arginine	chemical	This variance might be caused by an addition of 100 mM arginine before cell lysis to keep protein solubility and also by later replacement of arginine with 30% glycerol by dialysis.	RESULTS
142	150	arginine	chemical	This variance might be caused by an addition of 100 mM arginine before cell lysis to keep protein solubility and also by later replacement of arginine with 30% glycerol by dialysis.	RESULTS
160	168	glycerol	chemical	This variance might be caused by an addition of 100 mM arginine before cell lysis to keep protein solubility and also by later replacement of arginine with 30% glycerol by dialysis.	RESULTS
0	21	Structure comparisons	experimental_method	Structure comparisons	RESULTS
5	29	β-class N6 adenine MTase	protein_type	As a β-class N6 adenine MTase, the M1.HpyAVI structure displayed a good similarity with M.MboIIA (PDB ID 1G60) and M.RsrI (PDB ID 1NW7), which are falling into the same subgroup.	RESULTS
35	44	M1.HpyAVI	protein	As a β-class N6 adenine MTase, the M1.HpyAVI structure displayed a good similarity with M.MboIIA (PDB ID 1G60) and M.RsrI (PDB ID 1NW7), which are falling into the same subgroup.	RESULTS
45	54	structure	evidence	As a β-class N6 adenine MTase, the M1.HpyAVI structure displayed a good similarity with M.MboIIA (PDB ID 1G60) and M.RsrI (PDB ID 1NW7), which are falling into the same subgroup.	RESULTS
88	96	M.MboIIA	protein	As a β-class N6 adenine MTase, the M1.HpyAVI structure displayed a good similarity with M.MboIIA (PDB ID 1G60) and M.RsrI (PDB ID 1NW7), which are falling into the same subgroup.	RESULTS
115	121	M.RsrI	protein	As a β-class N6 adenine MTase, the M1.HpyAVI structure displayed a good similarity with M.MboIIA (PDB ID 1G60) and M.RsrI (PDB ID 1NW7), which are falling into the same subgroup.	RESULTS
0	15	Superimposition	experimental_method	Superimposition of M1.HpyAVI onto them gave RMSDs of 1.63 Å and 1.9 Å on 168 and 190 Cα atoms, respectively.	RESULTS
19	28	M1.HpyAVI	protein	Superimposition of M1.HpyAVI onto them gave RMSDs of 1.63 Å and 1.9 Å on 168 and 190 Cα atoms, respectively.	RESULTS
44	49	RMSDs	evidence	Superimposition of M1.HpyAVI onto them gave RMSDs of 1.63 Å and 1.9 Å on 168 and 190 Cα atoms, respectively.	RESULTS
67	70	TRD	structure_element	The most striking structural difference was found to locate on the TRD region (residues 133-163 in M1.HpyAVI) (Figure 3A–3C), where the secondary structures vary among these structures.	RESULTS
88	95	133-163	residue_range	The most striking structural difference was found to locate on the TRD region (residues 133-163 in M1.HpyAVI) (Figure 3A–3C), where the secondary structures vary among these structures.	RESULTS
99	108	M1.HpyAVI	protein	The most striking structural difference was found to locate on the TRD region (residues 133-163 in M1.HpyAVI) (Figure 3A–3C), where the secondary structures vary among these structures.	RESULTS
89	98	α-helices	structure_element	By comparison with the other two enzymes that possess protruding arms containing several α-helices and/or β-strands, the TRD of M1.HpyAVI is much shorter in length (Figure S1), wrapping more closely around the structural core and lacking apparent secondary structures.	RESULTS
106	115	β-strands	structure_element	By comparison with the other two enzymes that possess protruding arms containing several α-helices and/or β-strands, the TRD of M1.HpyAVI is much shorter in length (Figure S1), wrapping more closely around the structural core and lacking apparent secondary structures.	RESULTS
121	124	TRD	structure_element	By comparison with the other two enzymes that possess protruding arms containing several α-helices and/or β-strands, the TRD of M1.HpyAVI is much shorter in length (Figure S1), wrapping more closely around the structural core and lacking apparent secondary structures.	RESULTS
128	137	M1.HpyAVI	protein	By comparison with the other two enzymes that possess protruding arms containing several α-helices and/or β-strands, the TRD of M1.HpyAVI is much shorter in length (Figure S1), wrapping more closely around the structural core and lacking apparent secondary structures.	RESULTS
230	237	lacking	protein_state	By comparison with the other two enzymes that possess protruding arms containing several α-helices and/or β-strands, the TRD of M1.HpyAVI is much shorter in length (Figure S1), wrapping more closely around the structural core and lacking apparent secondary structures.	RESULTS
31	34	TRD	structure_element	Given the proposed role of the TRD for DNA interaction at the major groove, some differences of DNA recognition mode can be expected.	RESULTS
39	42	DNA	chemical	Given the proposed role of the TRD for DNA interaction at the major groove, some differences of DNA recognition mode can be expected.	RESULTS
62	74	major groove	structure_element	Given the proposed role of the TRD for DNA interaction at the major groove, some differences of DNA recognition mode can be expected.	RESULTS
96	99	DNA	chemical	Given the proposed role of the TRD for DNA interaction at the major groove, some differences of DNA recognition mode can be expected.	RESULTS
34	49	highly flexible	protein_state	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
50	54	loop	structure_element	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
63	65	β4	structure_element	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
70	72	αD	structure_element	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
83	88	33-58	residue_range	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
93	102	M1.HpyAVI	protein	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
131	141	structures	evidence	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
161	171	structures	evidence	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
175	183	M.MboIIA	protein	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
188	194	M.RsrI	protein	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
196	214	Sequence alignment	experimental_method	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
244	253	M1.HpyAVI	protein	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
351	360	H. pylori	species	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
373	381	flexible	protein_state	Another difference locates at the highly flexible loop between β4 and αD (residues 33-58) of M1.HpyAVI, which was invisible in our structures but present in the structures of M.MboIIA and M.RsrI. Sequence alignment revealed that this region of M1.HpyAVI was longer than its counterparts by 13 and 16 amino acids respectively, which likely renders the H. pylori enzyme more flexible.	RESULTS
0	22	Structural comparisons	experimental_method	Structural comparisons between M1.HpyAVI and other DNA MTases	FIG
31	40	M1.HpyAVI	protein	Structural comparisons between M1.HpyAVI and other DNA MTases	FIG
51	61	DNA MTases	protein_type	Structural comparisons between M1.HpyAVI and other DNA MTases	FIG
3	12	M1.HpyAVI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
17	25	M.MboIIA	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
30	36	M.RsrI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
41	49	TTHA0409	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
54	58	DpnM	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
63	69	M.TaqI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
71	80	M1.HpyAVI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
98	111	long disorder	protein_state	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
112	115	TRD	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
142	156	structure-rich	protein_state	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
157	160	TRD	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
164	172	M.MboIIA	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
174	180	M.RsrI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
185	193	TTHA0409	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
208	226	DNA-binding domain	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
230	234	DpnM	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
239	245	M.TaqI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
278	281	TRD	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
285	294	M1.HpyAVI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
296	304	M.MboIIA	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
306	312	M.RsrI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
317	325	TTHA0409	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
356	358	β4	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
363	365	αD	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
369	377	M.MboIIA	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
382	388	M.RsrI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
402	420	DNA-binding domain	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
424	428	DpnM	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
448	465	C-terminal domain	structure_element	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
469	475	M.TaqI	protein	A. M1.HpyAVI; B. M.MboIIA; C. M.RsrI; D. TTHA0409; E. DpnM; F. M.TaqI. M1.HpyAVI possesses only a long disorder TRD region, compared with the structure-rich TRD of M.MboIIA, M.RsrI and TTHA0409, or the extra DNA-binding domain of DpnM and M.TaqI. The core structure is in cyan; TRD of M1.HpyAVI, M.MboIIA, M.RsrI and TTHA0409 is in red; The region between β4 and αD of M.MboIIA and M.RsrI is in green; DNA-binding domain of DpnM is in magenta; The C-terminal domain of M.TaqI is in orange.	FIG
0	21	Structural comparison	experimental_method	Structural comparison between M1.HpyAVI and a putative β-class N4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) showed a good similarity as well, giving an RMSD of 1.73 Å on 164 Cα atoms (Figure 3D).	RESULTS
30	39	M1.HpyAVI	protein	Structural comparison between M1.HpyAVI and a putative β-class N4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) showed a good similarity as well, giving an RMSD of 1.73 Å on 164 Cα atoms (Figure 3D).	RESULTS
55	80	β-class N4 cytosine MTase	protein_type	Structural comparison between M1.HpyAVI and a putative β-class N4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) showed a good similarity as well, giving an RMSD of 1.73 Å on 164 Cα atoms (Figure 3D).	RESULTS
87	95	TTHA0409	protein	Structural comparison between M1.HpyAVI and a putative β-class N4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) showed a good similarity as well, giving an RMSD of 1.73 Å on 164 Cα atoms (Figure 3D).	RESULTS
154	158	RMSD	evidence	Structural comparison between M1.HpyAVI and a putative β-class N4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) showed a good similarity as well, giving an RMSD of 1.73 Å on 164 Cα atoms (Figure 3D).	RESULTS
81	84	TRD	structure_element	Exactly like the above comparison, the most significant difference exists in the TRD, where the structures vary in terms of length and presence of α-helices (Figure S1).	RESULTS
96	106	structures	evidence	Exactly like the above comparison, the most significant difference exists in the TRD, where the structures vary in terms of length and presence of α-helices (Figure S1).	RESULTS
147	156	α-helices	structure_element	Exactly like the above comparison, the most significant difference exists in the TRD, where the structures vary in terms of length and presence of α-helices (Figure S1).	RESULTS
0	9	M1.HpyAVI	protein	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
79	96	N6-adenine MTases	protein_type	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
132	139	α-class	protein_type	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
140	144	DpnM	protein	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
167	174	γ-class	protein_type	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
175	181	M.TaqI	protein	M1.HpyAVI displayed a considerable structural dissimilarity in comparison with N6-adenine MTases from other subgroups including the α-class DpnM (PDB ID 2DPM) and the γ-class M.TaqI (PDB ID 2ADM).	RESULTS
22	27	RMSDs	evidence	Both comparisons gave RMSDs above 3.0 Å (Figure 3E and 3F).	RESULTS
18	22	lack	protein_state	These two enzymes lack a counterpart loop present in the TRD of M1.HpyAVI, but instead rely on an extra domain for DNA binding and sequence recognition.	RESULTS
25	41	counterpart loop	structure_element	These two enzymes lack a counterpart loop present in the TRD of M1.HpyAVI, but instead rely on an extra domain for DNA binding and sequence recognition.	RESULTS
57	60	TRD	structure_element	These two enzymes lack a counterpart loop present in the TRD of M1.HpyAVI, but instead rely on an extra domain for DNA binding and sequence recognition.	RESULTS
64	73	M1.HpyAVI	protein	These two enzymes lack a counterpart loop present in the TRD of M1.HpyAVI, but instead rely on an extra domain for DNA binding and sequence recognition.	RESULTS
115	118	DNA	chemical	These two enzymes lack a counterpart loop present in the TRD of M1.HpyAVI, but instead rely on an extra domain for DNA binding and sequence recognition.	RESULTS
14	23	M1.HpyAVI	protein	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
36	51	long disordered	protein_state	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
52	55	TRD	structure_element	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
91	115	secondary structure-rich	protein_state	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
116	119	TRD	structure_element	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
129	169	β-class N6 adenine or N4 cytosine MTases	protein_type	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
213	223	DNA MTases	protein_type	Collectively, M1.HpyAVI possesses a long disordered TRD, which is in sharp contrast to the secondary structure-rich TRD in other β-class N6 adenine or N4 cytosine MTases or the extra DNA binding domain present in DNA MTases from other subgroups.	RESULTS
98	107	H. pylori	species	This striking difference may be a significant determinant of the wider substrate spectrum of this H. pylori enzyme.	RESULTS
0	21	AdoMet-binding pocket	site	AdoMet-binding pocket	RESULTS
4	27	cofactor binding pocket	site	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
31	40	M1.HpyAVI	protein	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
67	70	7-9	residue_range	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
72	77	29-31	residue_range	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
79	86	165-167	residue_range	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
88	95	216-218	residue_range	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
100	103	221	residue_number	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
127	136	conserved	protein_state	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
151	161	DNA MTases	protein_type	The cofactor binding pocket of M1.HpyAVI is surrounded by residues 7-9, 29-31, 165-167, 216-218 and 221 (Figure 4A), which are conserved among most of DNA MTases.	RESULTS
2	15	hydrogen bond	bond_interaction	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
24	27	D29	residue_name_number	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
35	50	catalytic motif	structure_element	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
51	55	DPPY	structure_element	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
79	84	bound	protein_state	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
85	91	AdoMet	chemical	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
114	119	MTase	protein_type	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
120	130	structures	evidence	A hydrogen bond between D29 in the catalytic motif DPPY and the amino group of bound AdoMet is preserved as other MTase structures.	RESULTS
9	11	D8	residue_name_number	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
16	18	A9	residue_name_number	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
24	38	hydrogen-bonds	bond_interaction	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
61	67	purine	chemical	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
92	96	E216	residue_name_number	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
113	129	hydrogen bonding	bond_interaction	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
163	169	ribose	chemical	Residues D8 and A9 from hydrogen-bonds with N6 and N1 of the purine ring, respectively, and E216 also locates at hydrogen bonding distance with O2′ and O3′ of the ribose.	RESULTS
13	17	H168	residue_name_number	In addition, H168, T200 and S198 contact the terminal carboxyl of AdoMet.	RESULTS
19	23	T200	residue_name_number	In addition, H168, T200 and S198 contact the terminal carboxyl of AdoMet.	RESULTS
28	32	S198	residue_name_number	In addition, H168, T200 and S198 contact the terminal carboxyl of AdoMet.	RESULTS
66	72	AdoMet	chemical	In addition, H168, T200 and S198 contact the terminal carboxyl of AdoMet.	RESULTS
0	13	Superposition	experimental_method	Superposition of M1.HpyAVI with the five structures shown in Figure 3 reveals that the orientation of cofactor is rather conserved except for M.TaqI (Figure 4B).	RESULTS
17	26	M1.HpyAVI	protein	Superposition of M1.HpyAVI with the five structures shown in Figure 3 reveals that the orientation of cofactor is rather conserved except for M.TaqI (Figure 4B).	RESULTS
41	51	structures	evidence	Superposition of M1.HpyAVI with the five structures shown in Figure 3 reveals that the orientation of cofactor is rather conserved except for M.TaqI (Figure 4B).	RESULTS
114	130	rather conserved	protein_state	Superposition of M1.HpyAVI with the five structures shown in Figure 3 reveals that the orientation of cofactor is rather conserved except for M.TaqI (Figure 4B).	RESULTS
142	148	M.TaqI	protein	Superposition of M1.HpyAVI with the five structures shown in Figure 3 reveals that the orientation of cofactor is rather conserved except for M.TaqI (Figure 4B).	RESULTS
34	39	bound	protein_state	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
61	67	M.TaqI	protein	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
97	107	absence of	protein_state	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
138	147	conserved	protein_state	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
148	154	AdoMet	chemical	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
169	174	FXGXG	structure_element	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
183	192	structure	evidence	The different conformation of the bound cofactor observed in M.TaqI might be attributable to the absence of corresponding residues of the conserved AdoMet-binding motif FXGXG in that structure.	RESULTS
0	35	Structural and biochemical analyses	experimental_method	Structural and biochemical analyses define two conserved residues D29 and E216 to be the key sites for AdoMet binding	FIG
47	56	conserved	protein_state	Structural and biochemical analyses define two conserved residues D29 and E216 to be the key sites for AdoMet binding	FIG
66	69	D29	residue_name_number	Structural and biochemical analyses define two conserved residues D29 and E216 to be the key sites for AdoMet binding	FIG
74	78	E216	residue_name_number	Structural and biochemical analyses define two conserved residues D29 and E216 to be the key sites for AdoMet binding	FIG
103	109	AdoMet	chemical	Structural and biochemical analyses define two conserved residues D29 and E216 to be the key sites for AdoMet binding	FIG
7	30	cofactor-binding cavity	site	A. The cofactor-binding cavity of M1.HpyAVI.	FIG
34	43	M1.HpyAVI	protein	A. The cofactor-binding cavity of M1.HpyAVI.	FIG
35	49	hydrogen bonds	bond_interaction	Residues (yellow) that form direct hydrogen bonds with AdoMet (green) are indicated, distance of the hydrogen bond is marked.	FIG
55	61	AdoMet	chemical	Residues (yellow) that form direct hydrogen bonds with AdoMet (green) are indicated, distance of the hydrogen bond is marked.	FIG
101	114	hydrogen bond	bond_interaction	Residues (yellow) that form direct hydrogen bonds with AdoMet (green) are indicated, distance of the hydrogen bond is marked.	FIG
3	16	Superposition	experimental_method	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
20	26	AdoMet	chemical	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
34	44	structures	evidence	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
48	57	M1.HpyAVI	protein	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
67	71	DpnM	protein	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
85	91	M.TaqI	protein	B. Superposition of AdoMet in the structures of M1.HpyAVI (green), DpnM (yellow) and M.TaqI (orange).	FIG
4	10	AdoMet	chemical	The AdoMet terminal carboxyl of M.TaqI reveals different orientations.	FIG
32	38	M.TaqI	protein	The AdoMet terminal carboxyl of M.TaqI reveals different orientations.	FIG
3	28	Cofactor binding affinity	evidence	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
32	34	wt	protein_state	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
36	43	mutants	protein_state	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
44	53	M1.HpyAVI	protein	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
75	100	microscale thermophoresis	experimental_method	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
102	105	MST	experimental_method	C. Cofactor binding affinity of wt-/mutants M1.HpyAVI proteins analyzed by microscale thermophoresis (MST).	FIG
4	20	binding affinity	evidence	The binding affinity was determined between fluorescently labelled M1.HpyAVI protein and unlabeled AdoMet.	FIG
67	76	M1.HpyAVI	protein	The binding affinity was determined between fluorescently labelled M1.HpyAVI protein and unlabeled AdoMet.	FIG
89	98	unlabeled	protein_state	The binding affinity was determined between fluorescently labelled M1.HpyAVI protein and unlabeled AdoMet.	FIG
99	105	AdoMet	chemical	The binding affinity was determined between fluorescently labelled M1.HpyAVI protein and unlabeled AdoMet.	FIG
0	6	AdoMet	chemical	AdoMet (15 nM to 1 mM) was titrated into a fixed concentration of M1.HpyAVI wt/mutant proteins (800 nM).	FIG
27	35	titrated	experimental_method	AdoMet (15 nM to 1 mM) was titrated into a fixed concentration of M1.HpyAVI wt/mutant proteins (800 nM).	FIG
66	75	M1.HpyAVI	protein	AdoMet (15 nM to 1 mM) was titrated into a fixed concentration of M1.HpyAVI wt/mutant proteins (800 nM).	FIG
76	78	wt	protein_state	AdoMet (15 nM to 1 mM) was titrated into a fixed concentration of M1.HpyAVI wt/mutant proteins (800 nM).	FIG
79	85	mutant	protein_state	AdoMet (15 nM to 1 mM) was titrated into a fixed concentration of M1.HpyAVI wt/mutant proteins (800 nM).	FIG
4	25	dissociation constant	evidence	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
27	29	KD	evidence	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
87	95	isotherm	evidence	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
121	130	M1.HpyAVI	protein	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
131	133	wt	protein_state	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
146	159	M1.HpyAVI-D8A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
174	188	M1.HpyAVI-D29A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
197	212	M1.HpyAVI-H168A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
228	243	M1.HpyAVI-S198A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
259	274	M1.HpyAVI-T200A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
290	305	M1.HpyAVI-E216A	mutant	The dissociation constant (KD) is yielded according to the law of mass action from the isotherm derived of the raw data: M1.HpyAVI-wt: 41 ± 6 μM; M1.HpyAVI-D8A :212 ± 11 μM; M1.HpyAVI-D29A : 0 μM; M1.HpyAVI-H168A : 471 ± 51 μM; M1.HpyAVI-S198A : 242 ± 32 μM; M1.HpyAVI-T200A : 252 ± 28 μM; M1.HpyAVI-E216A : 0 μM. Standard for three replicates is indicated.	FIG
3	24	DNA methyltransferase	protein_type	D. DNA methyltransferase activity of wide type protein and the mutants is quantified using radioactive assay.	FIG
37	46	wide type	protein_state	D. DNA methyltransferase activity of wide type protein and the mutants is quantified using radioactive assay.	FIG
63	70	mutants	protein_state	D. DNA methyltransferase activity of wide type protein and the mutants is quantified using radioactive assay.	FIG
91	108	radioactive assay	experimental_method	D. DNA methyltransferase activity of wide type protein and the mutants is quantified using radioactive assay.	FIG
0	11	[3H]-methyl	chemical	[3H]-methyl transferred to duplex DNA containing 5′-GAGG-3′ was quantified by Beckman LS6500 for 10 min, experiments were repeated for three times and data were corrected by subtraction of the background.	FIG
34	37	DNA	chemical	[3H]-methyl transferred to duplex DNA containing 5′-GAGG-3′ was quantified by Beckman LS6500 for 10 min, experiments were repeated for three times and data were corrected by subtraction of the background.	FIG
49	59	5′-GAGG-3′	chemical	[3H]-methyl transferred to duplex DNA containing 5′-GAGG-3′ was quantified by Beckman LS6500 for 10 min, experiments were repeated for three times and data were corrected by subtraction of the background.	FIG
3	16	Superposition	experimental_method	E. Superposition of M1.HpyAVI (green) with M.MboIIA (cyan) and M.RsrI (magenta).	FIG
20	29	M1.HpyAVI	protein	E. Superposition of M1.HpyAVI (green) with M.MboIIA (cyan) and M.RsrI (magenta).	FIG
43	51	M.MboIIA	protein	E. Superposition of M1.HpyAVI (green) with M.MboIIA (cyan) and M.RsrI (magenta).	FIG
63	69	M.RsrI	protein	E. Superposition of M1.HpyAVI (green) with M.MboIIA (cyan) and M.RsrI (magenta).	FIG
9	12	D29	residue_name_number	Residues D29 and E216 are conserved through all the DNA MTases mentioned in Figure 3 (not shown in Figure 4).	FIG
17	21	E216	residue_name_number	Residues D29 and E216 are conserved through all the DNA MTases mentioned in Figure 3 (not shown in Figure 4).	FIG
26	35	conserved	protein_state	Residues D29 and E216 are conserved through all the DNA MTases mentioned in Figure 3 (not shown in Figure 4).	FIG
52	62	DNA MTases	protein_type	Residues D29 and E216 are conserved through all the DNA MTases mentioned in Figure 3 (not shown in Figure 4).	FIG
72	86	single mutants	experimental_method	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
90	99	replacing	experimental_method	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
100	102	D8	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
104	107	D29	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
109	113	H168	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
115	119	S198	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
121	125	T200	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
127	131	E216	residue_name_number	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
137	144	alanine	residue_name	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
168	191	ligand binding affinity	evidence	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
198	223	microscale thermophoresis	experimental_method	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
225	228	MST	experimental_method	To confirm the key residues for ligand binding, we prepared a series of single mutants by replacing D8, D29, H168, S198, T200, E216 with alanine and investigated their ligand binding affinity using microscale thermophoresis (MST) assay.	RESULTS
42	51	wild type	protein_state	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
65	72	mutants	protein_state	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
105	107	KD	evidence	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
130	134	D29A	mutant	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
139	144	E216A	mutant	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
145	152	mutants	protein_state	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
166	189	protein-AdoMet affinity	evidence	As shown in Figure 4C, by contrast to the wild type enzyme, most mutants displayed variable reduction of KD value, among them the D29A and E216A mutants displayed no protein-AdoMet affinity at all.	RESULTS
31	45	hydrogen bonds	bond_interaction	The results suggested that the hydrogen bonds formed by D29 and E216 with AdoMet were most crucial interactions for cofactor binding.	RESULTS
56	59	D29	residue_name_number	The results suggested that the hydrogen bonds formed by D29 and E216 with AdoMet were most crucial interactions for cofactor binding.	RESULTS
64	68	E216	residue_name_number	The results suggested that the hydrogen bonds formed by D29 and E216 with AdoMet were most crucial interactions for cofactor binding.	RESULTS
74	80	AdoMet	chemical	The results suggested that the hydrogen bonds formed by D29 and E216 with AdoMet were most crucial interactions for cofactor binding.	RESULTS
0	8	Mutation	experimental_method	Mutation of the two residues may directly prevent the methyl transfer reaction of M1.HpyAVI.	RESULTS
54	60	methyl	chemical	Mutation of the two residues may directly prevent the methyl transfer reaction of M1.HpyAVI.	RESULTS
82	91	M1.HpyAVI	protein	Mutation of the two residues may directly prevent the methyl transfer reaction of M1.HpyAVI.	RESULTS
18	21	D29	residue_name_number	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
61	82	catalytic active site	site	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
83	87	DPPY	structure_element	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
105	109	E216	residue_name_number	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
155	164	conserved	protein_state	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
165	175	amino acid	chemical	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
187	193	MTases	protein_type	The importance of D29 is preserved because it belongs to the catalytic active site DPPY, but the residue E216 has not been fully investigated even being a conserved amino acid throughout MTases (Figure 4E).	RESULTS
0	4	E216	residue_name_number	E216 is the last residue of β2, which contacts the two hydroxyls of the ribose of AdoMet.	RESULTS
28	30	β2	structure_element	E216 is the last residue of β2, which contacts the two hydroxyls of the ribose of AdoMet.	RESULTS
72	78	ribose	chemical	E216 is the last residue of β2, which contacts the two hydroxyls of the ribose of AdoMet.	RESULTS
82	88	AdoMet	chemical	E216 is the last residue of β2, which contacts the two hydroxyls of the ribose of AdoMet.	RESULTS
0	11	Replacement	experimental_method	Replacement of this residue by alanine completely abolishes the key hydrogen bonds for AdoMet-binding, and very likely blocks the methyl transfer reaction.	RESULTS
31	38	alanine	residue_name	Replacement of this residue by alanine completely abolishes the key hydrogen bonds for AdoMet-binding, and very likely blocks the methyl transfer reaction.	RESULTS
68	82	hydrogen bonds	bond_interaction	Replacement of this residue by alanine completely abolishes the key hydrogen bonds for AdoMet-binding, and very likely blocks the methyl transfer reaction.	RESULTS
87	93	AdoMet	chemical	Replacement of this residue by alanine completely abolishes the key hydrogen bonds for AdoMet-binding, and very likely blocks the methyl transfer reaction.	RESULTS
130	136	methyl	chemical	Replacement of this residue by alanine completely abolishes the key hydrogen bonds for AdoMet-binding, and very likely blocks the methyl transfer reaction.	RESULTS
24	53	[3H]AdoMet radiological assay	experimental_method	To confirm this notion, [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the mutants.	RESULTS
82	88	methyl	chemical	To confirm this notion, [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the mutants.	RESULTS
114	121	mutants	protein_state	To confirm this notion, [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the mutants.	RESULTS
37	55	radiological assay	experimental_method	As shown in Figure 4D, the result of radiological assay agreed well with the MST measurement.	RESULTS
77	80	MST	experimental_method	As shown in Figure 4D, the result of radiological assay agreed well with the MST measurement.	RESULTS
4	8	D29A	mutant	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
13	18	E216A	mutant	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
19	26	mutants	protein_state	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
47	53	methyl	chemical	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
85	92	mutants	protein_state	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
111	128	methyltransferase	protein_type	The D29A and E216A mutants showed little or no methyl transfer activity, while other mutants exhibited reduced methyltransferase activity.	RESULTS
25	30	FXGXG	structure_element	As mentioned previously, FXGXG is a conserved AdoMet-binding motif of DNA MTases.	RESULTS
36	45	conserved	protein_state	As mentioned previously, FXGXG is a conserved AdoMet-binding motif of DNA MTases.	RESULTS
46	52	AdoMet	chemical	As mentioned previously, FXGXG is a conserved AdoMet-binding motif of DNA MTases.	RESULTS
70	80	DNA MTases	protein_type	As mentioned previously, FXGXG is a conserved AdoMet-binding motif of DNA MTases.	RESULTS
13	20	mutants	protein_state	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
25	30	FMGSG	structure_element	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
35	42	alanine	residue_name	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
53	63	amino acid	chemical	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
84	89	F195A	mutant	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
90	96	mutant	protein_state	We also made mutants of “FMGSG” to alanine for every amino acid, and found that the F195A mutant was insoluble probably due to decreasing the local hydrophobicity upon this mutation.	RESULTS
33	56	ligand binding affinity	evidence	We subsequently investigated the ligand binding affinity and methyl transfer reaction of the other mutants using MST and a radiological assay.	RESULTS
61	67	methyl	chemical	We subsequently investigated the ligand binding affinity and methyl transfer reaction of the other mutants using MST and a radiological assay.	RESULTS
99	106	mutants	protein_state	We subsequently investigated the ligand binding affinity and methyl transfer reaction of the other mutants using MST and a radiological assay.	RESULTS
113	116	MST	experimental_method	We subsequently investigated the ligand binding affinity and methyl transfer reaction of the other mutants using MST and a radiological assay.	RESULTS
123	141	radiological assay	experimental_method	We subsequently investigated the ligand binding affinity and methyl transfer reaction of the other mutants using MST and a radiological assay.	RESULTS
14	18	G197	residue_name_number	We found that G197 played a crucial role in AdoMet-binding, while mutagenesis of M196 and G199 did not influence cofactor binding and catalytic activity (Figure S2A and B).	RESULTS
44	50	AdoMet	chemical	We found that G197 played a crucial role in AdoMet-binding, while mutagenesis of M196 and G199 did not influence cofactor binding and catalytic activity (Figure S2A and B).	RESULTS
66	77	mutagenesis	experimental_method	We found that G197 played a crucial role in AdoMet-binding, while mutagenesis of M196 and G199 did not influence cofactor binding and catalytic activity (Figure S2A and B).	RESULTS
81	85	M196	residue_name_number	We found that G197 played a crucial role in AdoMet-binding, while mutagenesis of M196 and G199 did not influence cofactor binding and catalytic activity (Figure S2A and B).	RESULTS
90	94	G199	residue_name_number	We found that G197 played a crucial role in AdoMet-binding, while mutagenesis of M196 and G199 did not influence cofactor binding and catalytic activity (Figure S2A and B).	RESULTS
0	4	G197	residue_name_number	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
10	19	conserved	protein_state	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
43	53	DNA MTases	protein_type	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
59	68	replacing	experimental_method	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
72	79	alanine	residue_name	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
133	156	cofactor-binding pocket	site	G197 is a conserved residue throughout the DNA MTases, and replacing by alanine at this site likely change the local conformation of cofactor-binding pocket.	RESULTS
0	11	Mutagenesis	experimental_method	Mutagenesis on this glycine residue in M.EcoKI or M.EcoP15I also abolished the AdoMet-binding activity.	RESULTS
20	27	glycine	residue_name	Mutagenesis on this glycine residue in M.EcoKI or M.EcoP15I also abolished the AdoMet-binding activity.	RESULTS
39	46	M.EcoKI	protein	Mutagenesis on this glycine residue in M.EcoKI or M.EcoP15I also abolished the AdoMet-binding activity.	RESULTS
50	59	M.EcoP15I	protein	Mutagenesis on this glycine residue in M.EcoKI or M.EcoP15I also abolished the AdoMet-binding activity.	RESULTS
79	85	AdoMet	chemical	Mutagenesis on this glycine residue in M.EcoKI or M.EcoP15I also abolished the AdoMet-binding activity.	RESULTS
9	25	mutational study	experimental_method	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
53	57	F195	residue_name_number	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
107	112	F195A	mutant	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
113	119	mutant	protein_state	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
121	140	structural analysis	experimental_method	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
185	191	AdoMet	chemical	Although mutational study could not tell the role of F195 in ligand binding due to the insolubility of the F195A mutant, structural analysis suggested the importance of this residue in AdoMet-binding.	RESULTS
19	23	F195	residue_name_number	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
46	68	π-stacking interaction	bond_interaction	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
93	99	AdoMet	chemical	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
137	143	AdoMet	chemical	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
144	152	bound in	protein_state	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
157	163	pocket	site	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
167	176	M1.HpyAVI	protein	The phenyl ring of F195 forms a perpendicular π-stacking interaction with the purine ring of AdoMet, which stabilizes the orientation of AdoMet bound in the pocket of M1.HpyAVI (Figure S2C).	RESULTS
24	35	mutagenesis	experimental_method	In a separate scenario, mutagenesis of this residue in M.EcoRV has been proven to play an important role in AdoMet binding.	RESULTS
55	62	M.EcoRV	protein	In a separate scenario, mutagenesis of this residue in M.EcoRV has been proven to play an important role in AdoMet binding.	RESULTS
108	114	AdoMet	chemical	In a separate scenario, mutagenesis of this residue in M.EcoRV has been proven to play an important role in AdoMet binding.	RESULTS
10	27	DNA-binding sites	site	Potential DNA-binding sites	RESULTS
13	31	DNA binding region	site	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
35	44	M1.HpyAVI	protein	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
58	70	hairpin loop	structure_element	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
80	87	101-133	residue_range	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
94	97	TRD	structure_element	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
108	115	136-166	residue_range	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
124	139	highly flexible	protein_state	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
140	144	loop	structure_element	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
155	160	33-58	residue_range	The putative DNA binding region of M1.HpyAVI involves the hairpin loop (residue 101-133), the TRD (residues 136-166), and a highly flexible loop (residues 33-58).	RESULTS
4	16	hairpin loop	structure_element	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
25	27	β6	structure_element	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
32	34	β7	structure_element	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
58	67	conserved	protein_state	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
68	72	HRRY	structure_element	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
137	149	minor groove	structure_element	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
157	162	bound	protein_state	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
163	166	DNA	chemical	The hairpin loop between β6 and β7 strands that carries a conserved HRRY sequence signature in the middle is proposed to insert into the minor groove of the bound DNA.	RESULTS
23	26	TRD	structure_element	As aforementioned, the TRD of M1.HpyAVI shows striking difference from the other DNA MTases, and the relaxed specificity of substrate recognition may be at least partially attributable to the disordered TRD.	RESULTS
30	39	M1.HpyAVI	protein	As aforementioned, the TRD of M1.HpyAVI shows striking difference from the other DNA MTases, and the relaxed specificity of substrate recognition may be at least partially attributable to the disordered TRD.	RESULTS
81	91	DNA MTases	protein_type	As aforementioned, the TRD of M1.HpyAVI shows striking difference from the other DNA MTases, and the relaxed specificity of substrate recognition may be at least partially attributable to the disordered TRD.	RESULTS
192	202	disordered	protein_state	As aforementioned, the TRD of M1.HpyAVI shows striking difference from the other DNA MTases, and the relaxed specificity of substrate recognition may be at least partially attributable to the disordered TRD.	RESULTS
203	206	TRD	structure_element	As aforementioned, the TRD of M1.HpyAVI shows striking difference from the other DNA MTases, and the relaxed specificity of substrate recognition may be at least partially attributable to the disordered TRD.	RESULTS
17	32	highly flexible	protein_state	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
33	37	loop	structure_element	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
64	68	DPPY	structure_element	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
78	87	M1.HpyAVI	protein	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
110	126	electron density	evidence	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
159	164	loops	structure_element	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
172	184	AdoMet-bound	protein_state	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
185	195	structures	evidence	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
199	206	M.PvuII	protein	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
208	212	DpnM	protein	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
216	222	M.TaqI	protein	In addition, the highly flexible loop immediately following the DPPY motif in M1.HpyAVI was poorly defined in electron density, exactly like the corresponding loops in the AdoMet-bound structures of M.PvuII, DpnM or M.TaqI that were invisible either.	RESULTS
5	9	loop	structure_element	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
48	51	DNA	chemical	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
80	110	protein-DNA complex structures	evidence	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
114	120	M.TaqI	protein	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
136	142	M.HhaI	protein	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
161	169	M.HaeIII	protein	This loop, however, was largely stabilized upon DNA binding, as observed in the protein-DNA complex structures of M.TaqI (PDB ID 2IBS), M.HhaI (PDB ID 1MHT) and M.HaeIII (PDB ID 1DCT).	RESULTS
4	16	well-ordered	protein_state	The well-ordered loop in those structures directly contacts the flipping adenine and forms hydrogen bond with neighboring bases.	RESULTS
17	21	loop	structure_element	The well-ordered loop in those structures directly contacts the flipping adenine and forms hydrogen bond with neighboring bases.	RESULTS
31	41	structures	evidence	The well-ordered loop in those structures directly contacts the flipping adenine and forms hydrogen bond with neighboring bases.	RESULTS
73	80	adenine	residue_name	The well-ordered loop in those structures directly contacts the flipping adenine and forms hydrogen bond with neighboring bases.	RESULTS
91	104	hydrogen bond	bond_interaction	The well-ordered loop in those structures directly contacts the flipping adenine and forms hydrogen bond with neighboring bases.	RESULTS
50	54	loop	structure_element	These observations implied that the corresponding loop in other MTases, e.g. M1.HpyAVI, is likely responsible for reducing sequence recognition specificity and thus plays crucial roles in catalysis.	RESULTS
64	70	MTases	protein_type	These observations implied that the corresponding loop in other MTases, e.g. M1.HpyAVI, is likely responsible for reducing sequence recognition specificity and thus plays crucial roles in catalysis.	RESULTS
77	86	M1.HpyAVI	protein	These observations implied that the corresponding loop in other MTases, e.g. M1.HpyAVI, is likely responsible for reducing sequence recognition specificity and thus plays crucial roles in catalysis.	RESULTS
33	42	M1.HpyAVI	protein	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
75	91	N6 adenine MTase	protein_type	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
115	122	adenine	residue_name	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
126	136	5′-GAGG-3′	chemical	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
137	147	5′-GGAG-3′	chemical	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
160	168	adenines	residue_name	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
172	182	5′-GAAG-3′	chemical	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
258	265	adenine	residue_name	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
269	279	5′-GAGG-3′	chemical	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
295	304	M1.HpyAVI	protein	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
339	342	DNA	chemical	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
384	393	M1.HpyAVI	protein	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
421	430	H. pylori	species	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
443	470	multiple sequence alignment	experimental_method	Previous research suggested that M1.HpyAVI from strain 26695 was the first N6 adenine MTase that can methylate the adenine of 5′-GAGG-3′/5′-GGAG-3′ or both two adenines of 5′-GAAG-3′, compared with the homologs from other strains that can methylate only one adenine of 5′-GAGG-3′. To answer why M1.HpyAVI displayed a wider specificity for DNA recognition, we randomly choose fifty of M1.HpyAVI sequences from hundreds of H. pylori strains for multiple sequence alignment.	RESULTS
9	28	sequence comparison	experimental_method	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
33	52	structural analysis	experimental_method	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
78	81	P41	residue_name_number	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
83	87	N111	residue_name_number	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
89	93	K165	residue_name_number	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
98	102	T166	residue_name_number	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
121	129	replaced	experimental_method	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
133	139	serine	residue_name	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
141	150	threonine	residue_name	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
152	161	threonine	residue_name	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
166	172	valine	residue_name	Based on sequence comparison and structural analysis, four residues including P41, N111, K165 and T166 were selected and replaced by serine, threonine, threonine and valine, respectively (Figure 5A).	RESULTS
8	37	[3H]AdoMet radiological assay	experimental_method	Then, a [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the wide type protein and the mutants.	RESULTS
66	72	methyl	chemical	Then, a [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the wide type protein and the mutants.	RESULTS
98	107	wide type	protein_state	Then, a [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the wide type protein and the mutants.	RESULTS
124	131	mutants	protein_state	Then, a [3H]AdoMet radiological assay was applied to quantify the methyl transfer activity of the wide type protein and the mutants.	RESULTS
41	44	DNA	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
54	64	5′-GAGG-3′	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
68	79	5′-GAAG-3′,	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
88	95	mutants	protein_state	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
129	135	methyl	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
170	172	wt	protein_state	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
173	182	M1.HpyAVI	protein	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
222	233	5′-GGAG-3′,	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
238	244	methyl	chemical	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
270	274	P41S	mutant	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
275	281	mutant	protein_state	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
324	333	wild type	protein_state	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
334	343	M1.HpyAVI	protein	As shown in Figure 5, when the substrate DNA contains 5′-GAGG-3′ or 5′-GAAG-3′, all the mutants showed no apparent difference of methyl transfer activity compared to the wt-M1.HpyAVI; but when the recognition sequence was 5′-GGAG-3′, the methyl transfer activity of the P41S mutant was significantly reduced compared to the wild type M1.HpyAVI.	RESULTS
0	18	Sequence alignment	experimental_method	Sequence alignment, structural analysis and radioactive methyl transfer activity define the key residue for wider substrate specificity of M1.HpyAVI	FIG
20	39	structural analysis	experimental_method	Sequence alignment, structural analysis and radioactive methyl transfer activity define the key residue for wider substrate specificity of M1.HpyAVI	FIG
44	80	radioactive methyl transfer activity	experimental_method	Sequence alignment, structural analysis and radioactive methyl transfer activity define the key residue for wider substrate specificity of M1.HpyAVI	FIG
139	148	M1.HpyAVI	protein	Sequence alignment, structural analysis and radioactive methyl transfer activity define the key residue for wider substrate specificity of M1.HpyAVI	FIG
3	21	Sequence alignment	experimental_method	A. Sequence alignment of M1.HpyAVI from 50 H. pylori strains including 26695 revealed several variant residues.	FIG
25	34	M1.HpyAVI	protein	A. Sequence alignment of M1.HpyAVI from 50 H. pylori strains including 26695 revealed several variant residues.	FIG
43	52	H. pylori	species	A. Sequence alignment of M1.HpyAVI from 50 H. pylori strains including 26695 revealed several variant residues.	FIG
9	12	P41	residue_name_number	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
14	18	N111	residue_name_number	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
20	24	K165	residue_name_number	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
29	33	T166	residue_name_number	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
37	46	M1.HpyAVI	protein	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
59	64	26695	species	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
86	105	structural analysis	experimental_method	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
110	128	sequence alignment	experimental_method	Residues P41, N111, K165 and T166 of M1.HpyAVI from strain 26695 were chosen based on structural analysis and sequence alignment (shown in red arrow).	FIG
42	49	WebLogo	experimental_method	Amino-acid conservation is depicted using WebLogo (Crooks et al, 2004).	FIG
11	17	Methyl	chemical	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
58	60	wt	protein_state	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
61	70	M1.HpyAVI	protein	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
72	86	M1.HpyAVI-P41S	mutant	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
88	103	M1.HpyAVI-N111T	mutant	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
109	130	M1.HpyAVI-K165R T166V	mutant	B., C., D. Methyl transfer reactions were performed using wt-M1.HpyAVI, M1.HpyAVI-P41S, M1.HpyAVI-N111T, and M1.HpyAVI-K165R T166V, respectively.	FIG
43	46	DNA	chemical	Radioactivity incorporated into the duplex DNA containing 5′-GAGG-3′, 5′-GAAG-3′ or 5′-GGAG-3′ was quantified by Beckman LS6500 for 10 min.	FIG
58	68	5′-GAGG-3′	chemical	Radioactivity incorporated into the duplex DNA containing 5′-GAGG-3′, 5′-GAAG-3′ or 5′-GGAG-3′ was quantified by Beckman LS6500 for 10 min.	FIG
70	80	5′-GAAG-3′	chemical	Radioactivity incorporated into the duplex DNA containing 5′-GAGG-3′, 5′-GAAG-3′ or 5′-GGAG-3′ was quantified by Beckman LS6500 for 10 min.	FIG
84	94	5′-GGAG-3′	chemical	Radioactivity incorporated into the duplex DNA containing 5′-GAGG-3′, 5′-GAAG-3′ or 5′-GGAG-3′ was quantified by Beckman LS6500 for 10 min.	FIG
33	36	P41	residue_name_number	Our experimental data identified P41 as a key residue determining the recognition of GGAG of M1.HpyAVI.	RESULTS
85	89	GGAG	structure_element	Our experimental data identified P41 as a key residue determining the recognition of GGAG of M1.HpyAVI.	RESULTS
93	102	M1.HpyAVI	protein	Our experimental data identified P41 as a key residue determining the recognition of GGAG of M1.HpyAVI.	RESULTS
31	46	highly flexible	protein_state	This amino acid locates in the highly flexible loop between residues 33 and 58, which is involved in DNA binding and substrate recognition as shown above.	RESULTS
47	51	loop	structure_element	This amino acid locates in the highly flexible loop between residues 33 and 58, which is involved in DNA binding and substrate recognition as shown above.	RESULTS
69	78	33 and 58	residue_range	This amino acid locates in the highly flexible loop between residues 33 and 58, which is involved in DNA binding and substrate recognition as shown above.	RESULTS
101	104	DNA	chemical	This amino acid locates in the highly flexible loop between residues 33 and 58, which is involved in DNA binding and substrate recognition as shown above.	RESULTS
0	11	Replacement	experimental_method	Replacement by serine at this position definitely changes the local conformation and hydrophobicity, and probably some structural properties of the whole loop, which may in turn result in reduced specificity for sequence recognition of the enzyme from strain 26695.	RESULTS
15	21	serine	residue_name	Replacement by serine at this position definitely changes the local conformation and hydrophobicity, and probably some structural properties of the whole loop, which may in turn result in reduced specificity for sequence recognition of the enzyme from strain 26695.	RESULTS
154	158	loop	structure_element	Replacement by serine at this position definitely changes the local conformation and hydrophobicity, and probably some structural properties of the whole loop, which may in turn result in reduced specificity for sequence recognition of the enzyme from strain 26695.	RESULTS
259	264	26695	species	Replacement by serine at this position definitely changes the local conformation and hydrophobicity, and probably some structural properties of the whole loop, which may in turn result in reduced specificity for sequence recognition of the enzyme from strain 26695.	RESULTS
13	22	DNA-bound	protein_state	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
23	32	structure	evidence	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
64	88	γ-class N6-adenine MTase	protein_type	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
114	121	adenine	residue_name	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
141	144	DNA	chemical	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
167	173	methyl	chemical	Although the DNA-bound structure of previous investigation on a γ-class N6-adenine MTase revealed that the target adenine was rotated out of DNA helix, details of the methyl transfer process were still unclear.	DISCUSS
56	72	N6-methyladenine	ptm	Additionally, recent studies reported the importance of N6-methyladenine in some eukaryotic species, but until now there has not been any N6-adenine MTases being identified in eukaryotes.	DISCUSS
81	91	eukaryotic	taxonomy_domain	Additionally, recent studies reported the importance of N6-methyladenine in some eukaryotic species, but until now there has not been any N6-adenine MTases being identified in eukaryotes.	DISCUSS
138	155	N6-adenine MTases	protein_type	Additionally, recent studies reported the importance of N6-methyladenine in some eukaryotic species, but until now there has not been any N6-adenine MTases being identified in eukaryotes.	DISCUSS
176	186	eukaryotes	taxonomy_domain	Additionally, recent studies reported the importance of N6-methyladenine in some eukaryotic species, but until now there has not been any N6-adenine MTases being identified in eukaryotes.	DISCUSS
0	43	Biochemical and structural characterization	experimental_method	Biochemical and structural characterization of M1.HpyAVI provides a new model for uncovering the methyl transfer mechanism and for investigating the N6-methyladenine in eukaryotes.	DISCUSS
47	56	M1.HpyAVI	protein	Biochemical and structural characterization of M1.HpyAVI provides a new model for uncovering the methyl transfer mechanism and for investigating the N6-methyladenine in eukaryotes.	DISCUSS
97	103	methyl	chemical	Biochemical and structural characterization of M1.HpyAVI provides a new model for uncovering the methyl transfer mechanism and for investigating the N6-methyladenine in eukaryotes.	DISCUSS
149	165	N6-methyladenine	ptm	Biochemical and structural characterization of M1.HpyAVI provides a new model for uncovering the methyl transfer mechanism and for investigating the N6-methyladenine in eukaryotes.	DISCUSS
169	179	eukaryotes	taxonomy_domain	Biochemical and structural characterization of M1.HpyAVI provides a new model for uncovering the methyl transfer mechanism and for investigating the N6-methyladenine in eukaryotes.	DISCUSS
20	30	DNA MTases	protein_type	Oligomeric state of DNA MTases was long accepted as monomer, but our study indicated here that M1.HpyAVI exists as a dimer both in crystal and solution.	DISCUSS
52	59	monomer	oligomeric_state	Oligomeric state of DNA MTases was long accepted as monomer, but our study indicated here that M1.HpyAVI exists as a dimer both in crystal and solution.	DISCUSS
95	104	M1.HpyAVI	protein	Oligomeric state of DNA MTases was long accepted as monomer, but our study indicated here that M1.HpyAVI exists as a dimer both in crystal and solution.	DISCUSS
117	122	dimer	oligomeric_state	Oligomeric state of DNA MTases was long accepted as monomer, but our study indicated here that M1.HpyAVI exists as a dimer both in crystal and solution.	DISCUSS
131	138	crystal	evidence	Oligomeric state of DNA MTases was long accepted as monomer, but our study indicated here that M1.HpyAVI exists as a dimer both in crystal and solution.	DISCUSS
26	54	β-class DNA exocyclic MTases	protein_type	Interestingly, some other β-class DNA exocyclic MTases showed similar oligomeric state in crystal and in solution, indicating that dimer may be the functional state shared by a subgroup of DNA MTases.	DISCUSS
90	97	crystal	evidence	Interestingly, some other β-class DNA exocyclic MTases showed similar oligomeric state in crystal and in solution, indicating that dimer may be the functional state shared by a subgroup of DNA MTases.	DISCUSS
131	136	dimer	oligomeric_state	Interestingly, some other β-class DNA exocyclic MTases showed similar oligomeric state in crystal and in solution, indicating that dimer may be the functional state shared by a subgroup of DNA MTases.	DISCUSS
189	199	DNA MTases	protein_type	Interestingly, some other β-class DNA exocyclic MTases showed similar oligomeric state in crystal and in solution, indicating that dimer may be the functional state shared by a subgroup of DNA MTases.	DISCUSS
4	19	highly flexible	protein_state	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
37	42	33-58	residue_range	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
48	51	TRD	structure_element	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
62	69	133-163	residue_range	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
74	83	M1.HpyAVI	protein	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
114	117	DNA	chemical	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
121	144	minor and major grooves	structure_element	The highly flexible region (residues 33-58) and TRD (residues 133-163) of M1.HpyAVI are supposed to interact with DNA at minor and major grooves, respectively.	DISCUSS
12	15	P41	residue_name_number	And residue P41 might be a key residue partially determining the substrate spectrum of M1.HpyAVI.	DISCUSS
87	96	M1.HpyAVI	protein	And residue P41 might be a key residue partially determining the substrate spectrum of M1.HpyAVI.	DISCUSS
4	11	missing	protein_state	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
12	16	loop	structure_element	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
34	43	33 and 58	residue_range	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
53	56	DNA	chemical	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
81	87	stable	protein_state	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
139	145	M.TaqI	protein	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
147	162	Crystallization	experimental_method	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
166	179	M1.HpyAVI-DNA	complex_assembly	The missing loop between residues 33 and 58 may need DNA binding so as to form a stable conformation, which is similar to the condition of M.TaqI. Crystallization of M1.HpyAVI-DNA complex warrants future investigations, with the purpose of revealing the mechanism behind the wider substrate specificity of this enzyme.	DISCUSS
0	15	DNA methylation	ptm	DNA methylation plays an important role in bacterial pathogenicity.	DISCUSS
43	52	bacterial	taxonomy_domain	DNA methylation plays an important role in bacterial pathogenicity.	DISCUSS
0	23	DNA adenine methylation	ptm	DNA adenine methylation was known to regulate the expression of some virulence genes in bacteria including H.pylori.	DISCUSS
88	96	bacteria	taxonomy_domain	DNA adenine methylation was known to regulate the expression of some virulence genes in bacteria including H.pylori.	DISCUSS
107	115	H.pylori	species	DNA adenine methylation was known to regulate the expression of some virulence genes in bacteria including H.pylori.	DISCUSS
14	37	DNA adenine methylation	ptm	Inhibitors of DNA adenine methylation may have a broad antimicrobial action by targeting DNA adenine methyltransferase.	DISCUSS
89	118	DNA adenine methyltransferase	protein_type	Inhibitors of DNA adenine methylation may have a broad antimicrobial action by targeting DNA adenine methyltransferase.	DISCUSS
41	56	DNA methylation	ptm	As an important biological modification, DNA methylation directly influences bacterial survival.	DISCUSS
77	86	bacterial	taxonomy_domain	As an important biological modification, DNA methylation directly influences bacterial survival.	DISCUSS
0	11	Knockout of	experimental_method	Knockout of M1.HpyAVI largely prevents the growth of H. pylori.	DISCUSS
12	21	M1.HpyAVI	protein	Knockout of M1.HpyAVI largely prevents the growth of H. pylori.	DISCUSS
53	62	H. pylori	species	Knockout of M1.HpyAVI largely prevents the growth of H. pylori.	DISCUSS
13	22	H. pylori	species	Importantly, H. pylori is involved in 90% of all gastric malignancies.	DISCUSS
83	91	H.pylori	species	Appropriate antibiotic regimens could successfully cure gastric diseases caused by H.pylori infection.	DISCUSS
24	33	H. pylori	species	However, eradication of H. pylori infection remains a big challenge for the significantly increasing prevalence of its resistance to antibiotics.	DISCUSS
39	53	adenine MTases	protein_type	The development of new drugs targeting adenine MTases such as M1.HpyAVI offers a new opportunity for inhibition of H. pylori infection.	DISCUSS
62	71	M1.HpyAVI	protein	The development of new drugs targeting adenine MTases such as M1.HpyAVI offers a new opportunity for inhibition of H. pylori infection.	DISCUSS
115	124	H. pylori	species	The development of new drugs targeting adenine MTases such as M1.HpyAVI offers a new opportunity for inhibition of H. pylori infection.	DISCUSS
61	64	D29	residue_name_number	Residues that play crucial roles for catalytic activity like D29 or E216 may influence the H.pylori survival.	DISCUSS
68	72	E216	residue_name_number	Residues that play crucial roles for catalytic activity like D29 or E216 may influence the H.pylori survival.	DISCUSS
91	99	H.pylori	species	Residues that play crucial roles for catalytic activity like D29 or E216 may influence the H.pylori survival.	DISCUSS
32	48	highly conserved	protein_state	Small molecules targeting these highly conserved residues are likely to emerge less drug resistance.	DISCUSS
16	25	structure	evidence	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
29	38	M1.HpyAVI	protein	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
58	68	disordered	protein_state	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
69	72	TRD	structure_element	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
91	94	P41	residue_name_number	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
123	141	DNA binding region	site	In summary, the structure of M1.HpyAVI is featured with a disordered TRD and a key residue P41that located in the putative DNA binding region that may associate with the wider substrate specificity.	DISCUSS
9	12	D29	residue_name_number	Residues D29 and E216 were identified to play a crucial role in cofactor binding.	DISCUSS
17	21	E216	residue_name_number	Residues D29 and E216 were identified to play a crucial role in cofactor binding.	DISCUSS
13	30	crystal structure	evidence	As the first crystal structure of N6-adenine MTase in H.pylori, this model may shed light on design of new antibiotics to interfere the growth and pathogenesis of H.pylori in human.	DISCUSS
34	50	N6-adenine MTase	protein_type	As the first crystal structure of N6-adenine MTase in H.pylori, this model may shed light on design of new antibiotics to interfere the growth and pathogenesis of H.pylori in human.	DISCUSS
54	62	H.pylori	species	As the first crystal structure of N6-adenine MTase in H.pylori, this model may shed light on design of new antibiotics to interfere the growth and pathogenesis of H.pylori in human.	DISCUSS
163	171	H.pylori	species	As the first crystal structure of N6-adenine MTase in H.pylori, this model may shed light on design of new antibiotics to interfere the growth and pathogenesis of H.pylori in human.	DISCUSS
175	180	human	species	As the first crystal structure of N6-adenine MTase in H.pylori, this model may shed light on design of new antibiotics to interfere the growth and pathogenesis of H.pylori in human.	DISCUSS