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A new model for how O6-methylguanine-DNA methyltransferase binds DNA

✍ Scribed by Robin A. Vora; Anthony E. Pegg; Steven E. Ealick

Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
204 KB
Volume
32
Category
Article
ISSN
0887-3585

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✦ Synopsis

Human methyltransferase (hAT) catalyzes the transfer of an alkyl group from the 6-position of guanine to an active site Cys residue. The physiological role of hAT is the repair of alkylated guanine residues in DNA. However, the repair of methylated or chloroethylated guanine bases negates the effects of certain chemotherapeutic agents. A model of how hAT binds DNA might be useful in the design of compounds that could inactivate hAT. We have used computer modeling studies to generate such a model. The model utilizes a helix-loop-wing DNA binding motif found in Mu transposase. The model incorporates a flipped out guanine base in order to bring the methylated oxygen atom close to the active site Cys residue. The model is consistent with a variety of chemical and biochemical data.

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