Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase AAG

Albert Y. Lau; Michael D. Wyatt; Brian J. Glassner; Leona D. Samson; Tom Ellenberger

doi:10.1073/pnas.97.25.13573

Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase AAG

Albert Y. Lau, Michael D. Wyatt, Brian J. Glassner, Leona D. Samson, Tom Ellenberger

Biochemistry and Molecular Biophysics

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

193 Scopus citations

Abstract

The human 3-methyladenine DNA glycosylase [alkyladenine DNA glycosylase (AAG)] catalyzes the first step of base excision repair by cleaving damaged bases from DNA. Unlike other DNA glycosylases that are specific for a particular type of damaged base, AAG excises a chemically diverse selection of substrate bases damaged by alkylation or deamination. The 2.1-A crystal structure of AAG complexed to DNA containing 1,N⁶-ethenoadenine suggests how modified bases can be distinguished from normal DNA bases in the enzyme active site. Mutational analyses of residues contacting the alkylated base in the crystal structures suggest that the shape of the damaged base, its hydrogen-bonding characteristics, and its aromaticity all contribute to the selective recognition of damage by AAG.

Original language	English
Pages (from-to)	13573-13578
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	97
Issue number	25
DOIs	https://doi.org/10.1073/pnas.97.25.13573
State	Published - Dec 5 2000

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title = "Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase AAG",

abstract = "The human 3-methyladenine DNA glycosylase [alkyladenine DNA glycosylase (AAG)] catalyzes the first step of base excision repair by cleaving damaged bases from DNA. Unlike other DNA glycosylases that are specific for a particular type of damaged base, AAG excises a chemically diverse selection of substrate bases damaged by alkylation or deamination. The 2.1-A crystal structure of AAG complexed to DNA containing 1,N6-ethenoadenine suggests how modified bases can be distinguished from normal DNA bases in the enzyme active site. Mutational analyses of residues contacting the alkylated base in the crystal structures suggest that the shape of the damaged base, its hydrogen-bonding characteristics, and its aromaticity all contribute to the selective recognition of damage by AAG.",

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Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase AAG. / Lau, Albert Y.; Wyatt, Michael D.; Glassner, Brian J.; Samson, Leona D.; Ellenberger, Tom.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 25, 05.12.2000, p. 13573-13578.

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

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AB - The human 3-methyladenine DNA glycosylase [alkyladenine DNA glycosylase (AAG)] catalyzes the first step of base excision repair by cleaving damaged bases from DNA. Unlike other DNA glycosylases that are specific for a particular type of damaged base, AAG excises a chemically diverse selection of substrate bases damaged by alkylation or deamination. The 2.1-A crystal structure of AAG complexed to DNA containing 1,N6-ethenoadenine suggests how modified bases can be distinguished from normal DNA bases in the enzyme active site. Mutational analyses of residues contacting the alkylated base in the crystal structures suggest that the shape of the damaged base, its hydrogen-bonding characteristics, and its aromaticity all contribute to the selective recognition of damage by AAG.

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