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

Roben A. Vora; Anthony E. Pegg; Steven E. Ealick

doi:10.1002/(SICI)1097-0134(19980701)32:1<3::AID-PROT2>3.0.CO;2-O

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

Roben A. Vora, Anthony E. Pegg, Steven E. Ealick

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3-6
Number of pages	4
Journal	Proteins: Structure, Function and Genetics
Volume	32
Issue number	1
DOIs	https://doi.org/10.1002/(SICI)1097-0134(19980701)32:1<3::AID-PROT2>3.0.CO;2-O
State	Published - Jul 1 1998

All Science Journal Classification (ASJC) codes

Structural Biology
Biochemistry
Molecular Biology

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10.1002/(SICI)1097-0134(19980701)32:1<3::AID-PROT2>3.0.CO;2-O

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title = "A new model for how O6-methylguanine-DNA methyltransferase binds DNA",

abstract = "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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AU - Pegg, Anthony E.

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N2 - 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.

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

Abstract

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