DB code: D00080

RLCP classification	3.747.29000.21 : Transfer
CATH domain	3.40.50.150 : Rossmann fold	Catalytic domain
CATH domain	3.90.220.10 : Adenine-n6-DNA-methyltransferase TaqI; Chain A, domain 2
E.C.	2.1.1.72
CSA	2adm
M-CSA	2adm
MACiE	M0046

CATH domain	Related DB codes (homologues)
3.40.50.150 : Rossmann fold	S00637 S00639 S00262 S00261 S00291 S00412 D00075 D00076 D00079 D00082 D00083 D00823

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
P14385	Modification methylase TaqI	M.TaqI EC 2.1.1.72 Adenine-specific methyltransferase TaqI	PF12950 (TaqI_C) [Graphical View]

KEGG enzyme name
site-specific DNA-methyltransferase (adenine-specific) modification methylase restriction-modification system

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P14385	MTTA_THEAQ	S-adenosyl-L-methionine + DNA adenine = S- adenosyl-L-homocysteine + DNA 6-methylaminopurine.

KEGG Pathways
Map code	Pathways	E.C.

Compound table
	Substrates		Products		Intermediates
KEGG-id	C00019	C00821	C00021	C03391
E.C.
Compound	S-Adenosyl-L-methionine	DNA adenine	S-Adenosyl-L-homocysteine	DNA 6-methylaminopurine
Type	amino acids,amine group,nucleoside,sulfonium ion	amine group,nucleic acids	amino acids,amine group,nucleoside,sulfide group	amine group,nucleic acids
ChEBI	67040 67040		16680 57856 16680 57856
PubChem	34755 34755		25246222 439155 25246222 439155

1admA01	Bound:SAM	Unbound	Unbound	Unbound
1admB01	Bound:SAM	Unbound	Unbound	Unbound
1aqiA01	Unbound	Unbound	Bound:SAH	Unbound
1aqiB01	Unbound	Unbound	Bound:SAH	Unbound
1aqjA01	Analogue:SFG	Unbound	Unbound	Unbound
1aqjB01	Analogue:SFG	Unbound	Unbound	Unbound
1g38A01	Unbound	Bound:_DA_606(chain B)	Analogue:NEA	Unbound
1g38D01	Unbound	Bound:_DA_606(chain E)	Analogue:NEA	Unbound
2admA01	Bound:SAM	Unbound	Unbound	Unbound
2admB01	Bound:SAM	Unbound	Unbound	Unbound
1admA02	Unbound	Unbound	Unbound	Unbound
1admB02	Unbound	Unbound	Unbound	Unbound
1aqiA02	Unbound	Unbound	Unbound	Unbound
1aqiB02	Unbound	Unbound	Unbound	Unbound
1aqjA02	Unbound	Unbound	Unbound	Unbound
1aqjB02	Unbound	Unbound	Unbound	Unbound
1g38A02	Unbound	Unbound	Unbound	Unbound
1g38D02	Unbound	Unbound	Unbound	Unbound
2admA02	Unbound	Unbound	Unbound	Unbound
2admB02	Unbound	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1admA01	ASN 105;TYR 108			PRO 106
1admB01	ASN 105;TYR 108			PRO 106
1aqiA01	ASN 105;TYR 108			PRO 106
1aqiB01	ASN 105;TYR 108			PRO 106
1aqjA01	ASN 105;TYR 108			PRO 106
1aqjB01	ASN 105;TYR 108			PRO 106
1g38A01	ASN 105;TYR 108			PRO 106
1g38D01	ASN 105;TYR 108			PRO 106
2admA01
2admB01
1admA02
1admB02
1aqiA02
1aqiB02
1aqjA02
1aqjB02
1g38A02
1g38D02
2admA02
2admB02

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[2]	p.134
[5]	p.63
[6]	p.124

References
[1]
Resource
Comments
Medline ID
PubMed ID	8070417
Journal	EMBO J
Year	1994
Volume	13(16)
Pages	3902-8
Authors	Willcock DF, Dryden DT, Murray NE
Title	A mutational analysis of the two motifs common to adenine methyltransferases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	7971991
Journal	Proc Natl Acad Sci U S A
Year	1994
Volume	91(23)
Pages	10957-61
Authors	Labahn J, Granzin J, Schluckebier G, Robinson DP, Jack WE, Schildkraut I, Saenger W
Title	Three-dimensional structure of the adenine-specific DNA methyltransferase M.Taq I in complex with the cofactor S-adenosylmethionine.
Related PDB	1adm
Related UniProtKB	P14385
[3]
Resource
Comments
Medline ID
PubMed ID	7607476
Journal	Gene
Year	1995
Volume	157(1-2)
Pages	131-4
Authors	Schluckebier G, Labahn J, Granzin J, Schildkraut I, Saenger W
Title	A model for DNA binding and enzyme action derived from crystallographic studies of the TaqI N6-adenine-methyltransferase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	7897657
Journal	J Mol Biol
Year	1995
Volume	247(1)
Pages	16-20
Authors	Schluckebier G, O'Gara M, Saenger W, Cheng X
Title	Universal catalytic domain structure of AdoMet-dependent methyltransferases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	8995524
Journal	J Mol Biol
Year	1997
Volume	265(1)
Pages	56-67
Authors	Schluckebier G, Kozak M, Bleimling N, Weinhold E, Saenger W
Title	Differential binding of S-adenosylmethionine S-adenosylhomocysteine and Sinefungin to the adenine-specific DNA methyltransferase M.TaqI.
Related PDB	1aqi 1aqj 2adm
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	11175899
Journal	Nat Struct Biol
Year	2001
Volume	8(2)
Pages	121-5
Authors	Goedecke K, Pignot M, Goody RS, Scheidig AJ, Weinhold E
Title	Structure of the N6-adenine DNA methyltransferase M.TaqI in complex with DNA and a cofactor analog.
Related PDB	1g38
Related UniProtKB

Comments
According to the literature [5] & [6], this enzyme catalyzes a direct methyl transfer to the acceptor amine group, adenine N6. Although acceptor groups are usually activated by general bases, the activation mechanism of this enzyme and the role of general base are very unique, according to the literature [6]. (1) The sidechain of Asn105 and mainchain carbonyl oxygen of Pro106 seem to activate and enhance the nucleophilicity of the acceptor amine group, adenine N6, by increasing the electron density of the acceptor group, and by assisting its hybridization change from sp2 towards sp3. (2) Thus, the acceptor group would be in a position for an inline attack on the methyl group of another substrate, SAM. (3) The resulting tetrahedral methyl-ammonium group intermediate would be stabilized by the hydrogen bonds to Asn105 and Pro106. Moreover, the positively charged intermediate and transtion state could be stabilized by cation-pi interactions with the electron-rich aromatic ring of Tyr108. (4) As the pKa of the methyl-ammonium group reduces dramatically, the sidechain of Asn105 and the mainchain of Pro106 could deprotonate the methyl-ammonium intermediate as general bases, which would complete the catalytic reaction.

Comments

According to the literature [5] & [6], this enzyme catalyzes a direct methyl transfer to the acceptor amine group, adenine N6. Although acceptor groups are usually activated by general bases, the activation mechanism of this enzyme and the role of general base are very unique, according to the literature [6].
(1) The sidechain of Asn105 and mainchain carbonyl oxygen of Pro106 seem to activate and enhance the nucleophilicity of the acceptor amine group, adenine N6, by increasing the electron density of the acceptor group, and by assisting its hybridization change from sp2 towards sp3.
(2) Thus, the acceptor group would be in a position for an inline attack on the methyl group of another substrate, SAM.
(3) The resulting tetrahedral methyl-ammonium group intermediate would be stabilized by the hydrogen bonds to Asn105 and Pro106. Moreover, the positively charged intermediate and transtion state could be stabilized by cation-pi interactions with the electron-rich aromatic ring of Tyr108.
(4) As the pKa of the methyl-ammonium group reduces dramatically, the sidechain of Asn105 and the mainchain of Pro106 could deprotonate the methyl-ammonium intermediate as general bases, which would complete the catalytic reaction.

Created	Updated
2002-08-13	2009-02-26