DB code: T00070

RLCP classification 1.40.6430.132 : Hydrolysis
CATH domain 3.30.310.20 : TATA-Binding Protein
1.10.340.30 : Endonuclease III; domain 1 Catalytic domain
1.10.1670.10 : Endonuclease Iii, domain 2 Catalytic domain
E.C. 3.2.2.21
CSA 1diz
M-CSA 1diz
MACiE M0313

CATH domain Related DB codes (homologues)
1.10.1670.10 : Endonuclease Iii, domain 2 D00511 D00266
1.10.340.30 : Endonuclease III; domain 1 S00749 D00511 D00266

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04395 DNA-3-methyladenine glycosylase 2
EC 3.2.2.21
3-methyladenine-DNA glycosylase II, inducible
TAG II
DNA-3-methyladenine glycosidase II
DNA-3-methyladenine glycosylase II
NP_416572.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490310.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF06029 (AlkA_N)
PF00730 (HhH-GPD)
[Graphical View]

KEGG enzyme name
DNA-3-methyladenine glycosidase II
Deoxyribonucleate 3-methyladenine glycosidase II
3-methyladenine DNA glycosylase II
DNA-3-methyladenine glycosidase II
AlkA

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04395 3MG2_ECOLI Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine, and 7-methyladenine. monomer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00871 C00001 C00913 C02230 C02242 C02241 C02270
E.C.
Compound Alkylated DNA H2O 3-Methyladenine 3-Methylguanine 7-Methylguanine 7-Methyladenine Base-removed DNA
Type nucleic acids H2O amine group,aromatic ring (with nitrogen atoms) amine group,aromatic ring (with nitrogen atoms) amide group,amine group,aromatic ring (with nitrogen atoms) amine group,aromatic ring (with nitrogen atoms) carbohydrate,nucleic acids,phosphate group/phosphate ion
ChEBI 15377
 15377
 		38635
 38635
 		27564
 46892
 46893
 27564
 46892
 46893
 		28664
 46894
 46897
 28664
 46894
 46897
 		28921
 28921
PubChem 22247451
 962
 22247451
 962
 		1673
 1673
 		76292
 76292
 		11361
 11361
 		71593
 71593
1dizA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dizB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mpgA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mpgB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pvsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pvsB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7D01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dizA02 Unbound Unbound Unbound Unbound Unbound Analogue:G-A-C-A-T-G-A-NRI-T-G-C-C-T (chain E) Unbound
1dizB02 Unbound Unbound Unbound Unbound Unbound Analogue:G-A-C-A-T-G-A-NRI-T-G-C-C-T (chain C) Unbound
1mpgA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mpgB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pvsA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pvsB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7D02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dizA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dizB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mpgA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mpgB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pvsA03 Unbound Unbound Unbound Analogue:7HP Unbound Unbound Unbound
1pvsB03 Unbound Unbound Unbound Analogue:7HP Unbound Unbound Unbound
3cvsA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvsD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cvtD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7A03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7B03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7C03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cw7D03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwaD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwtD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3cwuD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3d4vD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [1], [4] & Swiss-prot;P04395

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dizA01
1dizB01
1mpgA01
1mpgB01
1pvsA01
1pvsB01
3cvsA01
3cvsB01
3cvsC01
3cvsD01
3cvtA01
3cvtB01
3cvtC01
3cvtD01
3cw7A01
3cw7B01
3cw7C01
3cw7D01
3cwaA01
3cwaB01
3cwaC01
3cwaD01
3cwtA01
3cwtB01
3cwtC01
3cwtD01
3cwuA01
3cwuB01
3cwuC01
3cwuD01
3d4vA01
3d4vB01
3d4vC01
3d4vD01
1dizA02 TYR 222
1dizB02 TYR 222
1mpgA02 TYR 222
1mpgB02 TYR 222
1pvsA02 TYR 222
1pvsB02 TYR 222
3cvsA02 TYR 222
3cvsB02 TYR 222
3cvsC02 TYR 222
3cvsD02 TYR 222
3cvtA02 TYR 222
3cvtB02 TYR 222
3cvtC02 TYR 222
3cvtD02 TYR 222
3cw7A02 TYR 222
3cw7B02 TYR 222
3cw7C02 TYR 222
3cw7D02 TYR 222
3cwaA02 TYR 222
3cwaB02 TYR 222
3cwaC02 TYR 222
3cwaD02 TYR 222
3cwtA02 TYR 222
3cwtB02 TYR 222
3cwtC02 TYR 222
3cwtD02 TYR 222
3cwuA02 TYR 222
3cwuB02 TYR 222
3cwuC02 TYR 222
3cwuD02 TYR 222
3d4vA02 TYR 222
3d4vB02 TYR 222
3d4vC02 TYR 222
3d4vD02 TYR 222
1dizA03 ASP 238;TRP 272
1dizB03 ASP 238;TRP 272
1mpgA03 ASP 238;TRP 272
1mpgB03 ASP 238;TRP 272
1pvsA03 ASP 238;TRP 272
1pvsB03 ASP 238;TRP 272
3cvsA03 ASP 238;TRP 272
3cvsB03 ASP 238;TRP 272
3cvsC03 ASP 238;TRP 272
3cvsD03 ASP 238;TRP 272
3cvtA03 ASP 238;TRP 272
3cvtB03 ASP 238;TRP 272
3cvtC03 ASP 238;TRP 272
3cvtD03 ASP 238;TRP 272
3cw7A03 ASP 238;TRP 272
3cw7B03 ASP 238;TRP 272
3cw7C03 ASP 238;TRP 272
3cw7D03 ASP 238;TRP 272
3cwaA03 ASP 238;TRP 272
3cwaB03 ASP 238;TRP 272
3cwaC03 ASP 238;TRP 272
3cwaD03 ASP 238;TRP 272
3cwtA03 ASP 238;TRP 272
3cwtB03 ASP 238;TRP 272
3cwtC03 ASP 238;TRP 272
3cwtD03 ASP 238;TRP 272
3cwuA03 ASP 238;TRP 272
3cwuB03 ASP 238;TRP 272
3cwuC03 ASP 238;TRP 272
3cwuD03 ASP 238;TRP 272
3d4vA03 ASP 238;TRP 272
3d4vB03 ASP 238;TRP 272
3d4vC03 ASP 238;TRP 272
3d4vD03 ASP 238;TRP 272

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Figure 6
[4]
Fig. 5

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID
PubMed ID 8706136
Journal Cell
Year 1996
Volume 86
Pages 321-9
Authors Labahn J, Scharer OD, Long A, Ezaz-Nikpay K, Verdine GL, Ellenberger TE
Title Structural basis for the excision repair of alkylation-damaged DNA.
Related PDB 1mpg
Related UniProtKB P04395
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), MUTAGENESIS.
Medline ID
PubMed ID 8706135
Journal Cell
Year 1996
Volume 86
Pages 311-9
Authors Yamagata Y, Kato M, Odawara K, Tokuno Y, Nakashima Y, Matsushima N, Yasumura K, Tomita K, Ihara K, Fujii Y, Nakabeppu Y, Sekiguchi M, Fujii S
Title Three-dimensional structure of a DNA repair enzyme, 3-methyladenine DNA glycosylase II, from Escherichia coli.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10440863
Journal Bioessays
Year 1999
Volume 21
Pages 668-76
Authors Wyatt MD, Allan JM, Lau AY, Ellenberger TE, Samson LD
Title 3-methyladenine DNA glycosylases: structure, function, and biological importance.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10675345
Journal EMBO J
Year 2000
Volume 19
Pages 758-66
Authors Hollis T, Ichikawa Y, Ellenberger T
Title DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA.
Related PDB 1diz
Related UniProtKB P04395
[5]
Resource
Comments
Medline ID
PubMed ID 10946229
Journal Mutat Res
Year 2000
Volume 460
Pages 201-10
Authors Hollis T, Lau A, Ellenberger T
Title Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11223884
Journal Bioessays
Year 2001
Volume 23
Pages 270-81
Authors Scharer OD, Jiricny J
Title Recent progress in the biology, chemistry and structural biology of DNA glycosylases.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12009927
Journal Bioconjug Chem
Year 2002
Volume 13
Pages 403-7
Authors Teale M, Symersky J, DeLucas L
Title 3-methyladenine-DNA glycosylase II: the crystal structure of an AlkA-hypoxanthine complex suggests the possibility of product inhibition.
Related PDB 1pvs
Related UniProtKB P04395
[8]
Resource
Comments
Medline ID
PubMed ID 12848584
Journal Chem Rev
Year 2003
Volume 103
Pages 2729-59
Authors Stivers JT, Jiang YL
Title A mechanistic perspective on the chemistry of DNA repair glycosylases.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15126496
Journal J Biol Chem
Year 2004
Volume 279
Pages 26876-84
Authors O'Brien PJ, Ellenberger T
Title The Escherichia coli 3-methyladenine DNA glycosylase AlkA has a remarkably versatile active site.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 15941573
Journal Mutat Res
Year 2005
Volume 577
Pages 55-76
Authors Huffman JL, Sundheim O, Tainer JA
Title DNA base damage recognition and removal: new twists and grooves.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 18686953
Journal J Am Chem Soc
Year 2008
Volume 130
Pages 11570-1
Authors Lee S, Bowman BR, Ueno Y, Wang S, Verdine GL
Title Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine.
Related PDB 3d4v
Related UniProtKB P04395
[12]
Resource
Comments
Medline ID
PubMed ID 18682218
Journal Structure
Year 2008
Volume 16
Pages 1166-74
Authors Bowman BR, Lee S, Wang S, Verdine GL
Title Structure of the E. coli DNA glycosylase AlkA bound to the ends of duplex DNA: a system for the structure determination of lesion-containing DNA.
Related PDB 3cvs 3cvt 3cw7 3cwa 3cws 3cwt 3cwu
Related UniProtKB P04395
[13]
Resource
Comments
Medline ID
PubMed ID 19659577
Journal FEMS Microbiol Rev
Year 2009
Volume 33
Pages 1044-78
Authors Dalhus B, Laerdahl JK, Backe PH, Bjoras M
Title DNA base repair--recognition and initiation of catalysis.
Related PDB
Related UniProtKB

Comments
This enzyme is homologous to 3-methyladenine DNA glycosylase I (EC 3.2.2.20; S00749 in EzCatDB) and DNA-3-methyladenine glycosylase (EC 3.2.2.21; S00188 in EzCatDB). However, its active site and reaction mechanism seem to be different from those of the homologous enzymes.
According to the literature [4], this enzyme may catalyze the following reaction:
(1) As the carbocation transition state is formed, Asp238 stabilizes C1' atom of the ribose and Trp272 and Tyr222 stabilize the positively charged base.
(2) The bond between C1' and the base is cleaved (SN1-like reaction).
(3) The leaving base can act as a general base to deprotonate a nearby water.
(4) The activated water can make a nucleophilic attack on C1' atom to complete the reaction.

Created Updated
2010-08-02 2011-10-12