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Catalytic Site Atlas Search Results
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Catalytic Site Atlas

CSA LITERATURE entry for 1mud

E.C. nameADENINE GLYCOSYLASE
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.2.2.-
CSA Homologues of 1mudThere are 18 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number 3.2.2.-
PDBe Entry 1mud
PDBSum Entry 1mud
MACiE Entry 1mud

Literature Report

IntroductionOxidative DNA damage is caused by reactive oxygen species that are generated during aerobic respiration and immune response. The oxidative lesions in DNA caused are repaired by the base excision repair pathway. Hydroxyl radicals rapidly react with guanine C8 producing a steady state level of mutagenic 8-oxoguanines in cells. It also creates 8-oxo-GTP that, like 8-oxoguanines in DNA template, is often mispaired with adenine by replicative polymerases, creating A-T to C-G and G-C to T-A transversion mutations.
DNA glycosylase MutY recognises the mutational intermediate 8-oxoguanine-adenine mispair and excises adenine from the mispair. This causes an abasic site that is then processed by the multi-enzyme base excision repair pathway. The sequence of MutY is conserved from bacteria to human suggesting its fundamental importance in DNA repair. Mutations of MutY increases transversion frequencies and hence cancer susceptibility in human.
MutY belongs to the base excision repair glycosylases superfamily which includes both pure DNA glycosylases and DNA glycosylase/lyases. The most conserved structural element in this family is the Helix-hairpin-Helix (HhH) motif.
MechansimMutY removes mispaired adenine via a hydrolytic mechanism. Asp138 abstracts a proton from a bound water molecule, thus activating the water for attack on C1' of the target adenosine, while protonated Glu37 stabilises the developing transition state through a hydrogen bond to adenine N7.

Catalytic Sites for 1mud

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AsnA138138macie:sideChainIt acts as a base to deprotonate a water molecule to allow its attack on C1' of the targeted adenosine.
GluA3737macie:sideChainIt forms a hydrogen bond to adenine N7 to stabilise the transition state.

Literature References

Notes:
Guan Y
MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily.
Nat Struct Biol 1998 5 1058-1064
PubMed: 9846876
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