NAD⁺依赖性DNA连接酶的晶体结构：模块化结构及其功能意义
Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.
作者信息
Lee J Y, Chang C, Song H K, Moon J, Yang J K, Kim H K, Kwon S T, Suh S W
机构信息
Center for Molecular Catalysis, Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742.
出版信息
EMBO J. 2000 Mar 1;19(5):1119-29. doi: 10.1093/emboj/19.5.1119.
Abstract
DNA ligases catalyze the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor. Despite the difference in cofactor specificity and limited overall sequence similarity, the two classes of DNA ligase share basically the same catalytic mechanism. In this study, the crystal structure of an NAD(+)-dependent DNA ligase from Thermus filiformis, a 667 residue multidomain protein, has been determined by the multiwavelength anomalous diffraction (MAD) method. It reveals highly modular architecture and a unique circular arrangement of its four distinct domains. It also provides clues for protein flexibility and DNA-binding sites. A model for the multidomain ligase action involving large conformational changes is proposed.
摘要
DNA连接酶在DNA复制、修复和重组过程中催化双链DNA断裂处的关键连接步骤，利用ATP或NAD(+)作为辅因子。尽管辅因子特异性存在差异且整体序列相似性有限，但两类DNA连接酶基本共享相同的催化机制。在本研究中，丝状栖热菌中一种依赖NAD(+)的DNA连接酶（一种含667个残基的多结构域蛋白）的晶体结构已通过多波长反常衍射（MAD）方法确定。它揭示了高度模块化的结构及其四个不同结构域的独特环状排列。它还为蛋白质的灵活性和DNA结合位点提供了线索。提出了一个涉及大的构象变化的多结构域连接酶作用模型。
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