Product-assisted catalysis in base-excision DNA repair

被引：152

作者：

Fromme, JC

Bruner, SD

Yang, W

Karplus, M

Verdine, GL ^{[1
]}

机构：

[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[2] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

来源：

NATURE STRUCTURAL BIOLOGY | 2003年 / 10卷 / 03期

关键词：

D O I：

10.1038/nsb902

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of catalyzing no fewer than five sequential reaction steps using a single active site has been unknown. To help answer this, we report the structure of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine DNA glycosylase. This structure and supporting biochemical results reveal that the enzyme sequesters the excised lesion base and exploits it as a cofactor to participate in catalysis. To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction.

引用

页码：204 / 211

页数：8

共 49 条

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