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尿嘧啶-DNA糖基化酶——对一类重要的DNA修复酶家族的结构与功能研究

Uracil-DNA glycosylases-structural and functional perspectives on an essential family of DNA repair enzymes.

作者信息

Schormann N, Ricciardi R, Chattopadhyay D

机构信息

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 35294.

出版信息

Protein Sci. 2014 Dec;23(12):1667-85. doi: 10.1002/pro.2554. Epub 2014 Oct 25.

Abstract

Uracil-DNA glycosylases (UDGs) are evolutionarily conserved DNA repair enzymes that initiate the base excision repair pathway and remove uracil from DNA. The UDG superfamily is classified into six families based on their substrate specificity. This review focuses on the family I enzymes since these are the most extensively studied members of the superfamily. The structural basis for substrate specificity and base recognition as well as for DNA binding, nucleotide flipping and catalytic mechanism is discussed in detail. Other topics include the mechanism of lesion search and molecular mimicry through interaction with uracil-DNA glycosylase inhibitors. The latest studies and findings detailing structure and function in the UDG superfamily are presented.

摘要

尿嘧啶-DNA糖基化酶(UDGs)是进化上保守的DNA修复酶,它们启动碱基切除修复途径并从DNA中去除尿嘧啶。UDG超家族根据其底物特异性分为六个家族。本综述重点关注I类酶,因为它们是该超家族中研究最广泛的成员。详细讨论了底物特异性和碱基识别以及DNA结合、核苷酸翻转和催化机制的结构基础。其他主题包括损伤搜索机制以及通过与尿嘧啶-DNA糖基化酶抑制剂相互作用的分子模拟。本文介绍了有关UDG超家族结构和功能的最新研究和发现。

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