Georgescu Roxana E, Yurieva Olga, Kim Seung-Sup, Kuriyan John, Kong Xiang-Peng, O'Donnell Mike
The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, P. O. Box 228, New York, NY 10065, USA.
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11116-21. doi: 10.1073/pnas.0804754105. Epub 2008 Aug 4.
DNA polymerases attach to the DNA sliding clamp through a common overlapping binding site. We identify a small-molecule compound that binds the protein-binding site in the Escherichia coli beta-clamp and differentially affects the activity of DNA polymerases II, III, and IV. To understand the molecular basis of this discrimination, the cocrystal structure of the chemical inhibitor is solved in complex with beta and is compared with the structures of Pol II, Pol III, and Pol IV peptides bound to beta. The analysis reveals that the small molecule localizes in a region of the clamp to which the DNA polymerases attach in different ways. The results suggest that the small molecule may be useful in the future to probe polymerase function with beta, and that the beta-clamp may represent an antibiotic target.
DNA聚合酶通过一个共同的重叠结合位点附着于DNA滑动夹。我们鉴定出一种小分子化合物，它能结合大肠杆菌β夹中的蛋白质结合位点，并对DNA聚合酶II、III和IV的活性产生不同影响。为了解这种区分的分子基础，解析了该化学抑制剂与β形成的共晶体结构，并将其与结合到β上的Pol II、Pol III和Pol IV肽段的结构进行比较。分析表明，该小分子定位于夹中DNA聚合酶以不同方式附着的区域。结果表明，这种小分子未来可能有助于探究与β相关的聚合酶功能，并且β夹可能是一个抗生素作用靶点。
