Mechanism of inactivation of human O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine.

Human O 6 -alkylguanine-DNA alkyltransferase was rapidly inactivated by low concentrations of O 6 -benzylguanine, but the alkyltransferase from the Escherichia coli ogt gene was much less sensitive and alkyltransferases from the E. coli ada gene or from yeast were not affected. O 6 -Benzyl-2'-deoxyguanosine was less potent than the base, but was still an effective inactivator of the human alkyltransferase and had no effect on the microbial proteins. O 6 -Allylguanine was somewhat less active, but still gave complete inactivation of both the human and Ogt alkyltransferases at 200 μM in 30 min, slightly affected the Ada protein, and had no effect on the yeast alkyltransferase