期刊
NUCLEIC ACIDS RESEARCH
卷 41, 期 13, 页码 6761-6773出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt395
关键词
-
资金
- Spanish Ministry of Economy and Competitiveness [BFU2011-23645, BFU2011-24982]
- CONSOLIDER-INGENIO from the Spanish Ministry of Science and Innovation [CSD2007-00015]
- Fundacion Mutua Madrilena
- Madrid Autonomous Community [S2009MAT-1507]
- Fundacion Ramon Areces
- Spanish Ministry of Science and Innovation [BIO2010-20508-C04-03]
- Formacion de Profesorado Universitario Fellowship, Spanish Ministry of Education and Culture [AP2008-00916]
- CONSOLIDER-INGENIO [CSD2007-00015]
Uracil-DNA glycosylase (UDG) is a key repair enzyme responsible for removing uracil residues from DNA. Interestingly, UDG is the only enzyme known to be inhibited by two different DNA mimic proteins: p56 encoded by the Bacillus subtilis phage phi 29 and the well-characterized protein Ugi encoded by the B. subtilis phage PBS1/PBS2. Atomic-resolution crystal structures of the B. subtilis UDG both free and in complex with p56, combined with site-directed mutagenesis analysis, allowed us to identify the key amino acid residues required for enzyme activity, DNA binding and complex formation. An important requirement for complex formation is the recognition carried out by p56 of the protruding Phe191 residue from B. subtilis UDG, whose side-chain is inserted into the DNA minor groove to replace the flipped-out uracil. A comparative analysis of both p56 and Ugi inhibitors enabled us to identify their common and distinctive features. Thereby, our results provide an insight into how two DNA mimic proteins with different structural and biochemical properties are able to specifically block the DNA-binding domain of the same enzyme.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据