EzCatDB: T00070
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DB codeT00070
RLCP classification1.40.6430.132 : Hydrolysis
CATH domainDomain 13.30.310.20 : TATA-Binding Protein
Domain 21.10.340.30 : Endonuclease III; domain 1Catalytic domain
Domain 31.10.1670.10 : Endonuclease Iii, domain 2Catalytic domain
E.C.3.2.2.21
CSA1diz
MACiEM0313

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

Enzyme Name
UniProtKBKEGG

P04395
Protein nameDNA-3-methyladenine glycosylase 2DNA-3-methyladenine glycosidase II
Deoxyribonucleate 3-methyladenine glycosidase II
3-methyladenine DNA glycosylase II
DNA-3-methyladenine glycosidase II
AlkA
SynonymsEC 3.2.2.21
3-methyladenine-DNA glycosylase II, inducible
TAG II
DNA-3-methyladenine glycosidase II
DNA-3-methyladenine glycosylase II
RefSeqNP_416572.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490310.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PfamPF06029 (AlkA_N)
PF00730 (HhH-GPD)
[Graphical view]


UniProtKB:Accession NumberP04395
Entry name3MG2_ECOLI
ActivityHydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine, and 7-methyladenine.
Subunitmonomer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00871C00001C00913C02230C02242C02241C02270
CompoundAlkylated DNAH2O3-Methyladenine3-Methylguanine7-Methylguanine7-MethyladenineBase-removed DNA
Typenucleic acidsH2Oamine 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
38635
46893
46892
27564
46897
46894
28664
28921


PubChem
962
22247451
1673
76292
11361
71593


                
1dizA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1dizB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1mpgA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1mpgB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1pvsA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1pvsB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7A01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7B01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7C01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7D01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vA01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vB01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vC01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vD01Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1dizA02Unbound UnboundUnboundUnboundUnboundAnalogue:G-A-C-A-T-G-A-NRI-T-G-C-C-T(chain E)Unbound
1dizB02Unbound UnboundUnboundUnboundUnboundAnalogue:G-A-C-A-T-G-A-NRI-T-G-C-C-T(chain C)Unbound
1mpgA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1mpgB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1pvsA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1pvsB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7A02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7B02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7C02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7D02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vA02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vB02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vC02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vD02Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1dizA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1dizB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1mpgA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1mpgB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
1pvsA03Unbound UnboundUnboundAnalogue:7HPUnboundUnboundUnbound
1pvsB03Unbound UnboundUnboundAnalogue:7HPUnboundUnboundUnbound
3cvsA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvsD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cvtD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7A03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7B03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7C03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cw7D03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwaD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwtD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3cwuD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vA03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vB03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vC03Unbound UnboundUnboundUnboundUnboundUnboundUnbound
3d4vD03Unbound UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [1], [4] & Swiss-prot;P04395
pdbCatalytic residues
         
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       
1dizA02TYR 222
1dizB02TYR 222
1mpgA02TYR 222
1mpgB02TYR 222
1pvsA02TYR 222
1pvsB02TYR 222
3cvsA02TYR 222
3cvsB02TYR 222
3cvsC02TYR 222
3cvsD02TYR 222
3cvtA02TYR 222
3cvtB02TYR 222
3cvtC02TYR 222
3cvtD02TYR 222
3cw7A02TYR 222
3cw7B02TYR 222
3cw7C02TYR 222
3cw7D02TYR 222
3cwaA02TYR 222
3cwaB02TYR 222
3cwaC02TYR 222
3cwaD02TYR 222
3cwtA02TYR 222
3cwtB02TYR 222
3cwtC02TYR 222
3cwtD02TYR 222
3cwuA02TYR 222
3cwuB02TYR 222
3cwuC02TYR 222
3cwuD02TYR 222
3d4vA02TYR 222
3d4vB02TYR 222
3d4vC02TYR 222
3d4vD02TYR 222
1dizA03ASP 238;TRP 272
1dizB03ASP 238;TRP 272
1mpgA03ASP 238;TRP 272
1mpgB03ASP 238;TRP 272
1pvsA03ASP 238;TRP 272
1pvsB03ASP 238;TRP 272
3cvsA03ASP 238;TRP 272
3cvsB03ASP 238;TRP 272
3cvsC03ASP 238;TRP 272
3cvsD03ASP 238;TRP 272
3cvtA03ASP 238;TRP 272
3cvtB03ASP 238;TRP 272
3cvtC03ASP 238;TRP 272
3cvtD03ASP 238;TRP 272
3cw7A03ASP 238;TRP 272
3cw7B03ASP 238;TRP 272
3cw7C03ASP 238;TRP 272
3cw7D03ASP 238;TRP 272
3cwaA03ASP 238;TRP 272
3cwaB03ASP 238;TRP 272
3cwaC03ASP 238;TRP 272
3cwaD03ASP 238;TRP 272
3cwtA03ASP 238;TRP 272
3cwtB03ASP 238;TRP 272
3cwtC03ASP 238;TRP 272
3cwtD03ASP 238;TRP 272
3cwuA03ASP 238;TRP 272
3cwuB03ASP 238;TRP 272
3cwuC03ASP 238;TRP 272
3cwuD03ASP 238;TRP 272
3d4vA03ASP 238;TRP 272
3d4vB03ASP 238;TRP 272
3d4vC03ASP 238;TRP 272
3d4vD03ASP 238;TRP 272

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Figure 6
[4]Fig. 5

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
PubMed ID8706136
JournalCell
Year1996
Volume86
Pages321-9
AuthorsLabahn J, Scharer OD, Long A, Ezaz-Nikpay K, Verdine GL, Ellenberger TE
TitleStructural basis for the excision repair of alkylation-damaged DNA.
Related PDB1mpg
Related UniProtKBP04395
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), MUTAGENESIS.
PubMed ID8706135
JournalCell
Year1996
Volume86
Pages311-9
AuthorsYamagata 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
TitleThree-dimensional structure of a DNA repair enzyme, 3-methyladenine DNA glycosylase II, from Escherichia coli.
[3]
PubMed ID10440863
JournalBioessays
Year1999
Volume21
Pages668-76
AuthorsWyatt MD, Allan JM, Lau AY, Ellenberger TE, Samson LD
Title3-methyladenine DNA glycosylases: structure, function, and biological importance.
[4]
PubMed ID10675345
JournalEMBO J
Year2000
Volume19
Pages758-66
AuthorsHollis T, Ichikawa Y, Ellenberger T
TitleDNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA.
Related PDB1diz
Related UniProtKBP04395
[5]
PubMed ID10946229
JournalMutat Res
Year2000
Volume460
Pages201-10
AuthorsHollis T, Lau A, Ellenberger T
TitleStructural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase.
[6]
PubMed ID11223884
JournalBioessays
Year2001
Volume23
Pages270-81
AuthorsScharer OD, Jiricny J
TitleRecent progress in the biology, chemistry and structural biology of DNA glycosylases.
[7]
PubMed ID12009927
JournalBioconjug Chem
Year2002
Volume13
Pages403-7
AuthorsTeale M, Symersky J, DeLucas L
Title3-methyladenine-DNA glycosylase II: the crystal structure of an AlkA-hypoxanthine complex suggests the possibility of product inhibition.
Related PDB1pvs
Related UniProtKBP04395
[8]
PubMed ID12848584
JournalChem Rev
Year2003
Volume103
Pages2729-59
AuthorsStivers JT, Jiang YL
TitleA mechanistic perspective on the chemistry of DNA repair glycosylases.
[9]
PubMed ID15126496
JournalJ Biol Chem
Year2004
Volume279
Pages26876-84
AuthorsO'Brien PJ, Ellenberger T
TitleThe Escherichia coli 3-methyladenine DNA glycosylase AlkA has a remarkably versatile active site.
[10]
PubMed ID15941573
JournalMutat Res
Year2005
Volume577
Pages55-76
AuthorsHuffman JL, Sundheim O, Tainer JA
TitleDNA base damage recognition and removal: new twists and grooves.
[11]
PubMed ID18686953
JournalJ Am Chem Soc
Year2008
Volume130
Pages11570-1
AuthorsLee S, Bowman BR, Ueno Y, Wang S, Verdine GL
TitleSynthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine.
Related PDB3d4v
Related UniProtKBP04395
[12]
PubMed ID18682218
JournalStructure
Year2008
Volume16
Pages1166-74
AuthorsBowman BR, Lee S, Wang S, Verdine GL
TitleStructure 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 PDB3cvs,3cvt,3cw7,3cwa,3cws,3cwt,3cwu
Related UniProtKBP04395
[13]
PubMed ID19659577
JournalFEMS Microbiol Rev
Year2009
Volume33
Pages1044-78
AuthorsDalhus B, Laerdahl JK, Backe PH, Bjoras M
TitleDNA base repair--recognition and initiation of catalysis.

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.

createdupdated
2010-08-022011-10-12


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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