Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases
Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases
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DOI：
10.1016/j.jmb.2003.11.049
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发表时间：
2004-01-30
影响因子：
5.6
通讯作者：
Dumas, P
中科院分区：
文献类型：
--
作者：
Burnouf, DY;Olieric, V;Dumas, P
大多数DNA聚合酶通过小肽与其同源的进行性复制因子相互作用，这种相互作用是它们在体内发挥功能所绝对需要的。我们已经解决了大肠杆菌的β滑动夹和Pol IV（P16）的16个残基C-末端肽之间的复合物的晶体结构。七个C-末端残基与位于一个β单体表面的口袋结合。该区域先前被鉴定为另一种β钳结合蛋白的结合位点，即γ复合物的8亚基。我们表明，肽P16竞争性地防止β-钳介导的刺激的Pol IV和亚基DNA聚合酶的活动，这表明与β的α亚基的相互作用的网站是相同的，或重叠的Pol IV。δ、Pol IV和α亚基的这种共同结合位点显示由许多细菌β同系物中高度保守的残基形成，从而定义了滑动夹配体的进化上保守的疏水缝隙和抗生素药物设计的新靶点。(C)2003爱思唯尔有限公司。保留所有权利。
Most DNA polymerases interact with their cognate processive replication factor through a small peptide, this interaction being absolutely required for their function in vivo. We have solved the crystal structure of a complex between the beta sliding clamp of Escherichia coli and the 16 residue C-terminal peptide of Pol IV (P16). The seven C-terminal residues bind to a pocket located at the surface of one beta monomer. This region was previously identified as the binding site of another beta clamp binding protein, the 8 subunit of the gamma complex. We show that peptide P16 competitively prevents beta-clamp-mediated stimulation of both Pol IV and a subunit DNA polymerase activities, suggesting that the site of interaction of the alpha subunit with beta is identical with, or overlaps that of Pol IV. This common binding site for delta, Pol IV and alpha subunit is shown to be formed by residues that are highly conserved among many bacterial beta homologs, thus defining an evolutionarily conserved hydrophobic crevice for sliding clamp ligands and a new target for antibiotic drug design. (C) 2003 Elsevier Ltd. All rights reserved.