Reaction: (1) DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
(2) DNA (containing 4-O-methylthymine) + protein L-cysteine = DNA (without 4-O-methylthymine) + protein S-methyl-L-cysteine
Other name(s): ada (gene name); ogt (gene name); MGT1 (gene name); MGMT (gene name)
Systematic name: DNA-6-O-methylguanine/DNA-4-O-methylthymine:[protein]-L-cysteine S-methyltransferase
Comments: This protein is involved in the repair of methylated DNA. Unlike EC 3.2.2.20, DNA-3-methyladenine glycosidase I and EC 3.2.2.21, DNA-3-methyladenine glycosidase II, which remove the methylated base leaving an apurinic/apyrimidinic site, this enzyme transfers the methyl group from the methylated DNA to an internal cysteine residue, leaving an intact nucleotide. Since the methyl transfer is irreversible, the enzyme can only catalyse a single turnover.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 77271-19-3
References:
1. Foote, R.S., Mitra, S. and Pal, B.C. Demethylation of O6-methylguanine in a synthetic DNA polymer by an inducible activity in Escherichia coli. Biochem. Biophys. Res. Commun. 97 (1980) 654-659. [PMID: 7008792]
2. Olsson, M. and Lindehl, T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J. Biol. Chem. 255 (1980) 10569-10571. [PMID: 7000780]
3. McCarthy, T.V. and Lindahl, T. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli. Nucleic Acids Res. 13 (1985) 2683-2698. [PMID: 2987862]
4. Potter, P.M., Wilkinson, M.C., Fitton, J., Carr, F.J., Brennand, J., Cooper, D.P. and Margison, G.P. Characterisation and nucleotide sequence of ogt, the O6-alkylguanine-DNA-alkyltransferase gene of E. coli. Nucleic Acids Res. 15 (1987) 9177-9193. [PMID: 2825131]
5. Rebeck, G.W., Smith, C.M., Goad, D.L. and Samson, L. Characterization of the major DNA repair methyltransferase activity in unadapted Escherichia coli and identification of a similar activity in Salmonella typhimurium. J. Bacteriol. 171 (1989) 4563-4568. [PMID: 2670886]
6. Koike, G., Maki, H., Takeya, H., Hayakawa, H. and Sekiguchi, M. Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase. J. Biol. Chem. 265 (1990) 14754-14762. [PMID: 2394694]
7. Sassanfar, M., Dosanjh, M.K., Essigmann, J.M. and Samson, L. Relative efficiencies of the bacterial, yeast, and human DNA methyltransferases for the repair of O6-methylguanine and O4-methylthymine. Suggestive evidence for O4-methylthymine repair by eukaryotic methyltransferases. J. Biol. Chem. 266 (1991) 2767-2771. [PMID: 1993655]
8. Xiao, W., Derfler, B., Chen, J. and Samson, L. Primary sequence and biological functions of a Saccharomyces cerevisiae O6-methylguanine/O4-methylthymine DNA repair methyltransferase gene. EMBO J. 10 (1991) 2179-2186. [PMID: 2065659]