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Catalytic Site Atlas

CSA LITERATURE entry for 1cqg

E.C. nameDNA-(apurinic or apyrimidinic site) lyase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1cqgThere are 221 Homologs
CSA Entries With UniProtID P27695
CSA Entries With EC Number
PDBe Entry 1cqg
PDBSum Entry 1cqg
MACiE Entry 1cqg

Literature Report

IntroductionThioredoxin reduces disulfide bonds, for example the Ref-1 redox protein involved in the control of DNA transcription in humans. It is part of the thioredoxin family of enzymes with the conserved CXXC motif, occurring in both oxidised (disulfide) and reduced (dithiol) forms, depending on where in the redox cycle it is.
MechansimCys 32 is a thiolate and therefore nucleophilic; it attacks a sulphur of the substrate disulfide bond. This forms a mixed disulfide and breaks the original substrate disulfide bond, presumably in an SN2 reaction.
Cys 35 also has an unusually low pKa and attacks Cys 32 in another SN2 reaction; this creates a disulfide bond between Cys 32 and Cys 35, at the same time breaking the mixed disulfide bond between enzyme and substrate in another SN2 reaction.

Catalytic Sites for 1cqg

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AlaA3535macie:sideChainCys 35 breaks the mixed disulfide bond of the intermediate by attacking Cys 32 in an SN2 reaction.
CysA3232macie:sideChainExists as a nucleophilic thiolate, and breaks the substrate disulfide bond by attacking one of the sulphur atoms in an SN2 reaction.

Literature References

Notes:The low pKas of Cys 32 and Cys 35 has no definite cause; possible residues are Asp 26 (side chain), or the main chains of Trp 31, Gly 33 and Pro 34, which may all also be involved in proton shuffling between sulphur atoms of enzyme and substrate.
Qin J
The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal.
Structure 1996 4 613-620
PubMed: 8736558