MGMT binds alkylated DNA containing 6-O-methylguanine

Stable Identifier
R-HSA-5657651
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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MGMT recognizes and binds DNA containing 6-O-methylguanine in a manner consistent with a helix-loop-wing DNA binding model, where guanine is flipped out in order to bring the methylated oxygen atom close to MGMT active site (Vora et al. 1998, Daniels et al. 2000). Weakened or distorted base-pairs formed by 6-O-methylguanine probably aid in the substrate recognition by MGMT (Duguid et al. 2005). MGMT is stabilized by Zn2+ binding (Daniels et al. 2000).

Literature References
PubMed ID Title Journal Year
15964013 The structure of the human AGT protein bound to DNA and its implications for damage detection

Duguid, EM, Rice, PA, He, C

J. Mol. Biol. 2005
10747039 Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding

Daniels, DS, Mol, CD, Arvai, AS, Kanugula, S, Pegg, AE, Tainer, JA

EMBO J. 2000
8434121 Regulation of repair of alkylation damage in mammalian genomes.

Mitra, S, Kaina, B

Prog Nucleic Acid Res Mol Biol 1993
9672037 A new model for how O6-methylguanine-DNA methyltransferase binds DNA

Vora, RA, Pegg, AE, Ealick, SE

Proteins 1998
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