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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1k82

E.C. nameDNA-formamidopyrimidine glycosylase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.2.2.23
CSA Homologues of 1k82There are 37 Homologs
CSA Entries With UniProtID P05523
CSA Entries With EC Number 3.2.2.23
PDBe Entry 1k82
PDBSum Entry 1k82
MACiE Entry 1k82

Literature Report

IntroductionFormamidopyrimidine-DNA glycosylase is a bifunctional base excision repair enzyme - it has both DNA glycosylase and AP lyase activities - and is involved in removal of oxidised purines from oxidatively-damaged DNA in initiation of the base excision repair pathway.
MechansimFormamidopyrimidine-DNA glycosylase catalyses the hydrolysis of DNA. 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.
Nucelophilic attack at C1' of the deoxyribose sugar by Pro 1 and protonation of O4' by Glu 2 leads to base displacement and the opening of the deoxyribose ring. A Schiff base involving Pro 1 is formed with O4' stabilised by hydrogen bonding to Glu 2 and Arg 258. Lys 56 as a general base deprotonates C2', and then protonates the 3' phosphate leading to beta-elimination. Deprotonation of C4' is followed by protonation of the 5' phosphate by Arg 258 and the second beta-elimination.
Reaction

Catalytic Sites for 1k82

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA23macie:sideChainActs as a general acid catalyst and also stabilises the transition state.
LysA5657macie:sideChainActs as a general acid/base catalyst.
ProA12macie:sideChainNucleophilically attacks the deoxyribose ring to cause ring cleavage.
ArgA258259macie:sideChainActs as a general acid/base catalyst, and stabilises the transition state.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluB23macie:sideChainActs as a general acid catalyst and also stabilises the transition state.
LysB5657macie:sideChainActs as a general acid/base catalyst.
ProB12macie:sideChainNucleophilically attacks the deoxyribose ring to cause ring cleavage.
ArgB258259macie:sideChainActs as a general acid/base catalyst, and stabilises the transition state.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluC23macie:sideChainActs as a general acid catalyst and also stabilises the transition state.
LysC5657macie:sideChainActs as a general acid/base catalyst.
ProC12macie:sideChainNucleophilically attacks the deoxyribose ring to cause ring cleavage.
ArgC258259macie:sideChainActs as a general acid/base catalyst, and stabilises the transition state.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluD23macie:sideChainActs as a general acid catalyst and also stabilises the transition state.
LysD5657macie:sideChainActs as a general acid/base catalyst.
ProD12macie:sideChainNucleophilically attacks the deoxyribose ring to cause ring cleavage.
ArgD258259macie:sideChainActs as a general acid/base catalyst, and stabilises the transition state.

Literature References

Notes:
Sugahara M
Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8.
EMBO J 2000 19 3857-3869
PubMed: 10921868
Gilboa R
Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA.
J Biol Chem 2002 277 19811-19816
PubMed: 11912217
Zharkov DO
NH2-terminal proline acts as a nucleophile in the glycosylase/AP-lyase reaction catalyzed by Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) protein.
J Biol Chem 1997 272 5335-5341
PubMed: 9030608
Serre L
Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA.
EMBO J 2002 21 2854-2865
PubMed: 12065399
Lavrukhin OV
Involvement of phylogenetically conserved acidic amino acid residues in catalysis by an oxidative DNA damage enzyme formamidopyrimidine glycosylase.
Biochemistry 2000 39 15266-15271
PubMed: 11106507
Sidorkina OM
Role of lysine-57 in the catalytic activities of Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg protein).
Nucleic Acids Res 1998 26 5351-5357
PubMed: 9826758
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