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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1adn

E.C. namemethylated-DNA---[protein]-cysteine S-methyltransferase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 2.1.1.63
CSA Homologues of 1adn1eyf,1u8b,1wpk,1zgw,
CSA Entries With UniProtID P06134
CSA Entries With EC Number 2.1.1.63
PDBe Entry 1adn
PDBSum Entry 1adn
MACiE Entry M0295

Literature Report

IntroductionThe E. coli Ada protein is involved in the repair of alkylated DNA. It repairs methylphosphotriesters in DNA by direct, irreversible methyl transfer to one of its own cysteines. Since it reacts stoichiometrically with its substrate rather than catalytically it is referred to as a suicide enzyme. However, when it is methylated, it gains the ability to bind in a sequence-specific manner to DNA, and it can then activate the transcription of a methylation-resistance regulon.
MechansimThe zinc ion is involved not only in stabilisation of the protein structure but also in direct metalloactivation of the methyl acceptor residue. Coordination of Cys69 to the metal destabilises the thiol form and stabilises the corresponding thiolate, encouraging cysteine to be deprotonated and attack the methyl group of the methylphosphotriester in an SN2 reaction.
Reaction

Catalytic Sites for 1adn

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA6969macie:sideChainAttacks the methyl group of a methylphosphotriester in an SN2 reaction.

Literature References

Notes:
Myers LC
Solution structure of the DNA methyl phosphotriester repair domain of Escherichia coli Ada.
Biochemistry 1993 32 14089-14094
PubMed: 8260490
Myers LC
Repair of DNA methylphosphotriesters through a metalloactivated cysteine nucleophile.
Science 1993 261 1164-1167
PubMed: 8395079
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