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A new model for how O 6 ‐methylguanine‐DNA methyltransferase binds DNA
Author(s) -
Vora Robin A.,
Pegg Anthony E.,
Ealick Steven E.
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980701)32:1<3::aid-prot2>3.0.co;2-o
Subject(s) - guanine , dna , methyltransferase , chemistry , stereochemistry , active site , biochemistry , residue (chemistry) , docking (animal) , dna methyltransferase , methylation , enzyme , gene , nucleotide , medicine , nursing
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. Proteins 32:3–6, 1998. © 1998 Wiley‐Liss, Inc.