Mizushina Y, Sugawara F, Iida A, Sakaguchi K
Department of Applied Biological Science, Science University of Tokyo, Noda, Chiba, 278-8510, Japan.
J Mol Biol. 2000 Dec 1;304(3):385-95. doi: 10.1006/jmbi.2000.4223.
Unsaturated long-chain fatty acids selectively bind to the DNA binding sites of DNA polymerase beta and DNA topoisomerase II, and inhibit their activities, although the amino acid sequences of these enzymes are markedly different from each other. Computer modeling analysis revealed that the fatty acid interaction interface in both enzymes has a group of four amino acid residues in common, forming a pocket which binds to the fatty acid molecule. The four amino acid residues were Thr596, His735, Leu741 and Lys983 for yeast DNA topoisomerase II, corresponding to Thr79, His51, Leu11 and Lys35 for rat DNA polymerase beta. Using three-dimensional structure model analysis, we determined the spatial positioning of specific amino acid residues binding to the fatty acids in DNA topoisomerase II, and subsequently obtained supplementary information to build the structural model.
不饱和长链脂肪酸选择性地结合到DNA聚合酶β和DNA拓扑异构酶II的DNA结合位点，并抑制它们的活性，尽管这些酶的氨基酸序列彼此明显不同。计算机建模分析表明，两种酶中的脂肪酸相互作用界面有一组四个共同的氨基酸残基，形成一个与脂肪酸分子结合的口袋。酵母DNA拓扑异构酶II的四个氨基酸残基是Thr596、His735、Leu741和Lys983，对应于大鼠DNA聚合酶β的Thr79、His51、Leu11和Lys35。通过三维结构模型分析，我们确定了DNA拓扑异构酶II中与脂肪酸结合的特定氨基酸残基的空间定位，随后获得了构建结构模型的补充信息。
