Crystal structure of full length topoisomerase I from Thermotoga maritima
Crystal structure of full length topoisomerase I from Thermotoga maritima
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DOI：
10.1016/j.jmb.2006.03.012
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发表时间：
2006-05-19
影响因子：
5.6
通讯作者：
Reinemer, Peter
中科院分区：
文献类型：
--
作者：
Hansen, Guido;Harrenga, Axel;Reinemer, Peter
DNA拓扑异构酶是通过DNA的磷酸二酯骨架的协同断裂和重新连接来改变DNA拓扑结构的一类酶。细菌和原始型IA拓扑异构酶，包括拓扑异构酶I、拓扑异构酶III和反向旋转酶，在调节DNA超卷曲和维持遗传稳定性方面起着至关重要的作用。从1.7埃分辨率测定了来自海洋热水菌的全长拓扑异构酶I的晶体结构，代表了一个完整和完全活性的细菌拓扑异构酶I。揭示了保守的酯交换核心区的环状结构，包括I-IV区和与核心区IV区紧密相关的C-末端锌带区(V区)。Maritima拓扑异构酶1的功能活性不依赖于锌，这一点得到了晶体结构的进一步支持，因为没有锌离子与结构域V结合，然而，通过在四个与锌结合的半胱氨酸残基之间形成两个二硫键，保持了结构的完整性。根据结构和以前的生化发现，提出并讨论了结构域V在DNA结合和识别中的功能作用。此外，还提供了细菌拓扑异构酶I的含义。(C)2006爱思唯尔有限公司。保留所有权利。
DNA topoisomerases are a family of enzymes altering the topology of DNA by concerted breakage and rejoining of the phosphodiester backbone of DNA. Bacterial and archeal type IA topoisomerases, including topoisomerase I, topoisomerase III, and reverse gyrase, are crucial in regulation of DNA supercoiling and maintenance of genetic stability.The crystal structure of full length topoisomerase I from Thermotoga maritima was determined at 1.7 angstrom resolution and represents an intact and fully active bacterial topoisomerase I.It reveals the torus-like structure of the conserved transesterification core domain comprising domains I-IV and a tightly associated C-terminal zinc ribbon domain (domain V) packing against domain IV of the core domain. The previously established zinc-independence of the functional activity of T. maritima topoisomerase 1 is further supported by its crystal structure as no zinc ion is bound to domain V However, the structural integrity is preserved by the formation of two disulfide bridges between the four Zn-binding cysteine residues. A functional role of domain V in DNA binding and recognition is suggested and discussed in the light of the structure and previous biochemical findings. In addition, implications for bacterial topoisomerases I are provided. (c) 2006 Elsevier Ltd. All rights reserved.