Ada (protein)

Ada is an enzyme induced by treatment of bacterial cells with alkylating agents that mainly cause methylation damage. This phenomenon is called the adaptive response and hence the name. Ada is also called as O⁶ alkyl guanine transferase I (O⁶ AGT I) . Ada transfers the alkyl group from DNA bases and sugar-phosphate backbone to a cysteine residue inactivating itself. Consequently, it reacts stoichiometrically with its substrate rather than catalytically and is referred to as a suicide enzyme. Methylation of Ada protein converts it into a self transcriptional activator, inducing its own gene expression and the expression of other genes which together with Ada help the cells repair alkylation damage ^[2] . Ada removes the alkyl group attached to DNA bases like guanine (O⁶-alkyl guanine) or thymine (O⁴-alkyl thymine) and to the oxygen of the phosphodiester backbone of the DNA ^[1,3] . However, Ada shows greater preference for O⁶- alkyl guanine compared to either O⁴-thymine and alkylated phosphotriesters. Ada enzyme has two active sites, one for the alkylated guanines and thymines and the other for alkylated phosphotriesters ^[2] .

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References

1. Errol C. Friedberg, Graham C. Walker, Wolfram Siede, Richard D. Wood, Roger A. Schultz, Tom Ellenberger, DNA Repair and Mutagenesis, second edition, ASM press, ISBN 1-55581-319-4
2. Lindahl,T.,B. Sedgwick, M.Sekiguchi, & Y.Nakabeppu.(1988) Regulation and expression of adaptive response to alkylating agents, annu.Rev.Biochem.57:133-157
3. McCarthy,T.V., and T. Lindahl.(1985)Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E.Coli, Nucleic Acids Res.13:2683-2698