EzCatDB: S00430

DB codeS00430
CATH domainDomain 13.60.10.10Catalytic domain
E.C.4.2.99.18
CSA1bix

CATH domainRelated DB codes (homologues)
3.60.10.10S00428,S00429

Enzyme Name
Swiss-protKEGG

P27695
Protein nameDNA-(apurinic or apyrimidinic site) lyaseDNA-(apurinic or apyrimidinic site) lyase
AP lyase
AP endonuclease class I
endodeoxyribonuclease (apurinic or apyrimidinic)
deoxyribonuclease (apurinic or apyrimidinic)
E. coli endonuclease III
phage-T4 UV endonuclease
Micrococcus luteus UV endonuclease
AP site-DNA 5'-phosphomonoester-lyase
X-ray endonuclease III
SynonymsEC 4.2.99.18
Apurinic-apyrimidinic endonuclease 1
AP endonuclease 1
APEX nuclease
APEN
Protein REF-1


Swiss-prot:Accession NumberP27695
Entry nameAPEX1_HUMAN
ActivityThe C-O-P bond 3'' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3''-terminal unsaturated sugar and a product with a terminal 5''-phosphate.
SubunitMonomer. Component of the SET complex, which also contains SET, ANP32A, HMGB2 and NME1.
Subcellular locationNucleus.
Cofactor


CofactorsSubstratesProducts
KEGG-idC02148C02270C03484L00014C00039
CompoundDivalent metal(Magnesium or manganese)Base-removed DNAApyrimidinic site in DNAApurinic/Apyrimidinic site at DNA 5'-terminiDNA
Typedivalent metal (Ca2+, Mg2+)carbohydrate,nucleic acids,phosphate group/phosphate ionnucleic acidscarbohydrate,nucleic acids,phosphate group/phosphate ionnucleic acids
1bixAUnboundUnboundUnboundUnboundUnbound
1de8AUnboundUnboundAnalogue:G-C-T-A-C-3DR-G-A-T-C-G(chain U)UnboundUnbound
1de8BUnboundUnboundAnalogue:G-C-T-A-C-3DR-G-A-T-C-G(chain X)UnboundUnbound
1de9ABound:_MNUnboundUnboundBound:3DR-G-A-T-C(chain Y)Bound:C-T-A-C(chain X)
1de9BBound:_MNUnboundUnboundBound:3DR-G-A-T-C(chain V)Bound:C-T-A-C(chain U)
1dewAUnboundUnboundAnalogue:G-C-G-T-C-C-3DR-C-G-A-C-G-A-C-G(chain U)UnboundUnbound
1dewBUnboundUnboundAnalogue:G-C-G-T-C-C-3DR-C-G-A-C-G-A-C-G(chain X)UnboundUnbound
1e9nAUnboundUnboundUnboundUnboundUnbound
1e9nBUnboundUnboundUnboundUnboundUnbound
1hd7AUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P27695 & literature [14], [18], [25]
pdbCatalytic residuesCofactor-binding residues
1bixAASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1de8AASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1de8BASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1de9AASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1de9BASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1dewAASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1dewBASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1e9nAASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1e9nBASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)
1hd7AASN 174;ASP 210;ASN 212;ASP 283;HIS 309
ASP 70;GLU 96(Magnesium or manganese)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.7, p.65531
[6]p.4963-4964
[8]Fig.8, p.453-4541
[9]p.53-54
[14]Fig.3, p.4542
[18]Fig.5, p.1029-10311
[22]p.18-19
[25]Fig.1c, p.317-3201

references
[1]
PubMed ID8462727
JournalInt J Biochem
Year1993
Volume25
Pages359-66
AuthorsOno Y, Seki S, Akiyama K, Watanabe S, Furuta T, Ohmoto T
TitleExpression of a putative catalytic domain of the human APEX nuclease (a major apurinic/apyrimidinic endonuclease) in Escherichia coli.
[2]
CommentsMUTAGENESIS OF ASN-211.
Medline ID97086686
PubMed ID8932375
JournalNucleic Acids Res
Year1996
Volume24
Pages4217-21
AuthorsRothwell DG, Hickson ID
TitleAsparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1.
Related Swiss-protP27695
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 31-317.
Medline ID98063001
PubMed ID9351835
JournalEMBO J
Year1997
Volume16
Pages6548-58
AuthorsGorman MA, Morera S, Rothwell DG, de La Fortelle E, Mol CD, Tainer JA, Hickson ID, Freemont PS
TitleThe crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites.
Related PDB1bix
Related Swiss-protP27695
[4]
PubMed ID9804798
JournalJ Biol Chem
Year1998
Volume273
Pages30352-9
AuthorsMasuda Y, Bennett RA, Demple B
TitleDynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product.
[5]
PubMed ID10872450
JournalAnnu Rev Biochem
Year1999
Volume68
Pages255-85
AuthorsMcCullough AK, Dodson ML, Lloyd RS
TitleInitiation of base excision repair: glycosylase mechanisms and structures.
[6]
PubMed ID10213597
JournalBiochemistry
Year1999
Volume38
Pages4958-64
AuthorsLucas JA, Masuda Y, Bennett RA, Strauss NS, Strauss PR
TitleSingle-turnover analysis of mutant human apurinic/apyrimidinic endonuclease.
[7]
PubMed ID9867812
JournalJ Biol Chem
Year1999
Volume274
Pages67-74
AuthorsWaters TR, Gallinari P, Jiricny J, Swann PF
TitleHuman thymine DNA glycosylase binds to apurinic sites in DNA but is displaced by human apurinic endonuclease 1.
[8]
PubMed ID10390343
JournalJ Mol Biol
Year1999
Volume290
Pages447-57
AuthorsErzberger JP, Wilson DM 3rd
TitleThe role of Mg2+ and specific amino acid residues in the catalytic reaction of the major human abasic endonuclease: new insights from EDTA-resistant incision of acyclic abasic site analogs and site-directed mutagenesis.
[9]
PubMed ID10074406
JournalJ Mol Biol
Year1999
Volume287
Pages47-57
AuthorsIzumi T, Malecki J, Chaudhry MA, Weinfeld M, Hill JH, Lee JC, Mitra S
TitleIntragenic suppression of an active site mutation in the human apurinic/apyrimidinic endonuclease.
[10]
PubMed ID10962003
JournalJ Biol Chem
Year2000
Volume275
Pages37055-61
AuthorsWhisstock JC, Romero S, Gurung R, Nandurkar H, Ooms LM, Bottomley SP, Mitchell CA
TitleThe inositol polyphosphate 5-phosphatases and the apurinic/apyrimidinic base excision repair endonucleases share a common mechanism for catalysis.
[11]
PubMed ID10772862
JournalJ Mol Biol
Year2000
Volume298
Pages447-59
AuthorsNguyen LH, Barsky D, Erzberger JP, Wilson DM 3rd
TitleMapping the protein-DNA interface and the metal-binding site of the major human apurinic/apyrimidinic endonuclease.
[12]
PubMed ID10946228
JournalMutat Res
Year2000
Volume460
Pages183-99
AuthorsParikh SS, Putnam CD, Tainer JA
TitleLessons learned from structural results on uracil-DNA glycosylase.
[13]
PubMed ID10700268
JournalNat Struct Biol
Year2000
Volume7
Pages176-8
AuthorsWilson SH, Kunkel TA
TitlePassing the baton in base excision repair.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 39-317.
Medline ID20129262
PubMed ID10667800
JournalNature
Year2000
Volume403
Pages451-6
AuthorsMol CD, Izumi T, Mitra S, Tainer JA
TitleDNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination.
Related PDB1de8,1de9,1dew
Related Swiss-protP27695
[15]
PubMed ID11024165
JournalNucleic Acids Res
Year2000
Volume28
Pages3871-9
AuthorsHadi MZ, Coleman MA, Fidelis K, Mohrenweiser HW, Wilson DM 3rd
TitleFunctional characterization of Ape1 variants identified in the human population.
[16]
PubMed ID11683634
JournalBiochemistry
Year2001
Volume40
Pages13254-61
AuthorsMcKenzie JA, Strauss PR
TitleOligonucleotides with bistranded abasic sites interfere with substrate binding and catalysis by human apurinic/apyrimidinic endonuclease.
[17]
PubMed ID11707423
JournalEMBO J
Year2001
Volume20
Pages6530-9
AuthorsVidal AE, Boiteux S, Hickson ID, Radicella JP
TitleXRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions.
[18]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
Medline ID21184546
PubMed ID11286553
JournalJ Mol Biol
Year2001
Volume307
Pages1023-34
AuthorsBeernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B
TitleTwo divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism.
Related PDB1e9n,1hd7
Related Swiss-protP27695
[19]
PubMed ID12237116
JournalBiochem Biophys Res Commun
Year2002
Volume297
Pages288-93
AuthorsCao X, Kambe F, Ohmori S, Seo H
TitleOxidoreductive modification of two cysteine residues in paired domain by Ref-1 regulates DNA-binding activity of Pax-8.
[20]
PubMed ID11781104
JournalBiochemistry
Year2002
Volume41
Pages634-42
AuthorsDavid-Cordonnier MH, Cunniffe SM, Hickson ID, O'Neill P
TitleEfficiency of incision of an AP site within clustered DNA damage by the major human AP endonuclease.
[21]
PubMed ID11889047
JournalEMBO J
Year2002
Volume21
Pages1414-26
AuthorsChen J, Chiang YC, Denis CL
TitleCCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase.
[22]
PubMed ID12018403
JournalIUBMB Life
Year2002
Volume53
Pages15-23
AuthorsWhisstock JC, Wiradjaja F, Waters JE, Gurung R
TitleThe structure and function of catalytic domains within inositol polyphosphate 5-phosphatases.
[23]
PubMed ID11866537
JournalJ Mol Biol
Year2002
Volume316
Pages853-66
AuthorsHadi MZ, Ginalski K, Nguyen LH, Wilson DM 3rd
TitleDeterminants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III.
[24]
PubMed ID12547389
JournalDNA Repair (Amst)
Year2003
Volume2
Pages259-71
AuthorsMendez F, Sandigursky M, Kureekattil RP, Kenny MK, Franklin WA, Bases R
TitleSpecific stimulation of human apurinic/apyrimidinic endonuclease by heat shock protein 70.
[25]
PubMed ID12758078
JournalJ Mol Biol
Year2003
Volume329
Pages311-22
AuthorsLowry DF, Hoyt DW, Khazi FA, Bagu J, Lindsey AG, Wilson DM 3rd
TitleInvestigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1.

comments
Although this enzyme is classified as DNA-AP lyase, it catalyzes hydrolysis, instead of elimination, according to the literature. Thus, the products of this enzyme are different from those in other DNA-AP lyase (see D00266 in EzCatDB).
Cys65 has been speculated to be essential for redox activity (see [3]).

createdupdated
2004-07-212009-02-26


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 2010)
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)

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