DB code: S00430

CATH domain 3.60.10.10 : Deoxyribonuclease I; Chain A Catalytic domain
E.C. 4.2.99.18
CSA 1bix
M-CSA 1bix
MACiE

CATH domain Related DB codes (homologues)
3.60.10.10 : Deoxyribonuclease I; Chain A S00428 S00429

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
P27695 DNA-(apurinic or apyrimidinic site) lyase
EC 3.1.-.-
EC 4.2.99.18
APEX nuclease
APEN
Apurinic-apyrimidinic endonuclease 1
AP endonuclease 1
APE-1
REF-1
Redox factor-1
DNA-
(apurinic or apyrimidinic site)
lyase, mitochondrial
NP_001231178.1 (Protein)
NM_001244249.1 (DNA/RNA sequence)
NP_001632.2 (Protein)
NM_001641.3 (DNA/RNA sequence)
NP_542379.1 (Protein)
NM_080648.2 (DNA/RNA sequence)
NP_542380.1 (Protein)
NM_080649.2 (DNA/RNA sequence)
PF03372 (Exo_endo_phos)
[Graphical View]

KEGG enzyme name
DNA-(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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P27695 APEX1_HUMAN The 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. Monomer. Component of the SET complex, which also contains SET, ANP32A, HMGB2 and NME1. Nucleus.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C02148 C02270 C03484 L00014 C00039
E.C.
Compound Divalent metal(Magnesium or manganese) Base-removed DNA Apyrimidinic site in DNA Apurinic/Apyrimidinic site at DNA 5'-termini DNA
Type divalent metal (Ca2+, Mg2+) carbohydrate,nucleic acids,phosphate group/phosphate ion nucleic acids carbohydrate,nucleic acids,phosphate group/phosphate ion nucleic acids
ChEBI
PubChem
1bixA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1de8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:G-C-T-A-C-3DR-G-A-T-C-G (chain U) Unbound Unbound
1de8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:G-C-T-A-C-3DR-G-A-T-C-G (chain X) Unbound Unbound
1de9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MN Unbound Unbound Bound:3DR-G-A-T-C (chain Y) Bound:C-T-A-C (chain X)
1de9B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MN Unbound Unbound Bound:3DR-G-A-T-C (chain V) Bound:C-T-A-C (chain U)
1dewA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:G-C-G-T-C-C-3DR-C-G-A-C-G-A-C-G (chain U) Unbound Unbound
1dewB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:G-C-G-T-C-C-3DR-C-G-A-C-G-A-C-G (chain X) Unbound Unbound
1e9nA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e9nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1hd7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P27695 & literature [14], [18], [25]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bixA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1de8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1de8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1de9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1de9B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1dewA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1dewB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1e9nA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1e9nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)
1hd7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 174;ASP 210;ASN 212;ASP 283;HIS 309 ASP 70;GLU 96(Magnesium or manganese)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.7, p.6553 1
[6]
p.4963-4964
[8]
Fig.8, p.453-454 1
[9]
p.53-54
[14]
Fig.3, p.454 2
[18]
Fig.5, p.1029-1031 1
[22]
p.18-19
[25]
Fig.1c, p.317-320 1

References
[1]
Resource
Comments
Medline ID
PubMed ID 8462727
Journal Int J Biochem
Year 1993
Volume 25
Pages 359-66
Authors Ono Y, Seki S, Akiyama K, Watanabe S, Furuta T, Ohmoto T
Title Expression of a putative catalytic domain of the human APEX nuclease (a major apurinic/apyrimidinic endonuclease) in Escherichia coli.
Related PDB
Related UniProtKB
[2]
Resource
Comments MUTAGENESIS OF ASN-211.
Medline ID 97086686
PubMed ID 8932375
Journal Nucleic Acids Res
Year 1996
Volume 24
Pages 4217-21
Authors Rothwell DG, Hickson ID
Title Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1.
Related PDB
Related UniProtKB P27695
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 31-317.
Medline ID 98063001
PubMed ID 9351835
Journal EMBO J
Year 1997
Volume 16
Pages 6548-58
Authors Gorman MA, Morera S, Rothwell DG, de La Fortelle E, Mol CD, Tainer JA, Hickson ID, Freemont PS
Title The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites.
Related PDB 1bix
Related UniProtKB P27695
[4]
Resource
Comments
Medline ID
PubMed ID 9804798
Journal J Biol Chem
Year 1998
Volume 273
Pages 30352-9
Authors Masuda Y, Bennett RA, Demple B
Title Dynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10872450
Journal Annu Rev Biochem
Year 1999
Volume 68
Pages 255-85
Authors McCullough AK, Dodson ML, Lloyd RS
Title Initiation of base excision repair: glycosylase mechanisms and structures.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10213597
Journal Biochemistry
Year 1999
Volume 38
Pages 4958-64
Authors Lucas JA, Masuda Y, Bennett RA, Strauss NS, Strauss PR
Title Single-turnover analysis of mutant human apurinic/apyrimidinic endonuclease.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9867812
Journal J Biol Chem
Year 1999
Volume 274
Pages 67-74
Authors Waters TR, Gallinari P, Jiricny J, Swann PF
Title Human thymine DNA glycosylase binds to apurinic sites in DNA but is displaced by human apurinic endonuclease 1.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10390343
Journal J Mol Biol
Year 1999
Volume 290
Pages 447-57
Authors Erzberger JP, Wilson DM 3rd
Title The 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.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10074406
Journal J Mol Biol
Year 1999
Volume 287
Pages 47-57
Authors Izumi T, Malecki J, Chaudhry MA, Weinfeld M, Hill JH, Lee JC, Mitra S
Title Intragenic suppression of an active site mutation in the human apurinic/apyrimidinic endonuclease.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10962003
Journal J Biol Chem
Year 2000
Volume 275
Pages 37055-61
Authors Whisstock JC, Romero S, Gurung R, Nandurkar H, Ooms LM, Bottomley SP, Mitchell CA
Title The inositol polyphosphate 5-phosphatases and the apurinic/apyrimidinic base excision repair endonucleases share a common mechanism for catalysis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10772862
Journal J Mol Biol
Year 2000
Volume 298
Pages 447-59
Authors Nguyen LH, Barsky D, Erzberger JP, Wilson DM 3rd
Title Mapping the protein-DNA interface and the metal-binding site of the major human apurinic/apyrimidinic endonuclease.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10946228
Journal Mutat Res
Year 2000
Volume 460
Pages 183-99
Authors Parikh SS, Putnam CD, Tainer JA
Title Lessons learned from structural results on uracil-DNA glycosylase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10700268
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 176-8
Authors Wilson SH, Kunkel TA
Title Passing the baton in base excision repair.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 39-317.
Medline ID 20129262
PubMed ID 10667800
Journal Nature
Year 2000
Volume 403
Pages 451-6
Authors Mol CD, Izumi T, Mitra S, Tainer JA
Title DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination.
Related PDB 1de8 1de9 1dew
Related UniProtKB P27695
[15]
Resource
Comments
Medline ID
PubMed ID 11024165
Journal Nucleic Acids Res
Year 2000
Volume 28
Pages 3871-9
Authors Hadi MZ, Coleman MA, Fidelis K, Mohrenweiser HW, Wilson DM 3rd
Title Functional characterization of Ape1 variants identified in the human population.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11683634
Journal Biochemistry
Year 2001
Volume 40
Pages 13254-61
Authors McKenzie JA, Strauss PR
Title Oligonucleotides with bistranded abasic sites interfere with substrate binding and catalysis by human apurinic/apyrimidinic endonuclease.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11707423
Journal EMBO J
Year 2001
Volume 20
Pages 6530-9
Authors Vidal AE, Boiteux S, Hickson ID, Radicella JP
Title XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
Medline ID 21184546
PubMed ID 11286553
Journal J Mol Biol
Year 2001
Volume 307
Pages 1023-34
Authors Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B
Title Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism.
Related PDB 1e9n 1hd7
Related UniProtKB P27695
[19]
Resource
Comments
Medline ID
PubMed ID 12237116
Journal Biochem Biophys Res Commun
Year 2002
Volume 297
Pages 288-93
Authors Cao X, Kambe F, Ohmori S, Seo H
Title Oxidoreductive modification of two cysteine residues in paired domain by Ref-1 regulates DNA-binding activity of Pax-8.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11781104
Journal Biochemistry
Year 2002
Volume 41
Pages 634-42
Authors David-Cordonnier MH, Cunniffe SM, Hickson ID, O'Neill P
Title Efficiency of incision of an AP site within clustered DNA damage by the major human AP endonuclease.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11889047
Journal EMBO J
Year 2002
Volume 21
Pages 1414-26
Authors Chen J, Chiang YC, Denis CL
Title CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 12018403
Journal IUBMB Life
Year 2002
Volume 53
Pages 15-23
Authors Whisstock JC, Wiradjaja F, Waters JE, Gurung R
Title The structure and function of catalytic domains within inositol polyphosphate 5-phosphatases.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11866537
Journal J Mol Biol
Year 2002
Volume 316
Pages 853-66
Authors Hadi MZ, Ginalski K, Nguyen LH, Wilson DM 3rd
Title Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12547389
Journal DNA Repair (Amst)
Year 2003
Volume 2
Pages 259-71
Authors Mendez F, Sandigursky M, Kureekattil RP, Kenny MK, Franklin WA, Bases R
Title Specific stimulation of human apurinic/apyrimidinic endonuclease by heat shock protein 70.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12758078
Journal J Mol Biol
Year 2003
Volume 329
Pages 311-22
Authors Lowry DF, Hoyt DW, Khazi FA, Bagu J, Lindsey AG, Wilson DM 3rd
Title Investigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1.
Related PDB
Related UniProtKB

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]).

Created Updated
2004-07-21 2009-02-26