Crystal structure of an intact type II DNA topoisomerase: Insights into DNA transfer mechanisms
Crystal structure of an intact type II DNA topoisomerase: Insights into DNA transfer mechanisms
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DOI：
10.1016/j.str.2007.12.020
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
van Tilbeurgh, Herman
中科院分区：
文献类型：
--
作者：
Graille, Marc;Cladiere, Lionel;van Tilbeurgh, Herman
DNA拓扑异构酶解决在转录、复制和重组过程中产生的DNA拓扑问题。这些无处不在的酶对细胞存活至关重要，是开发抗菌和抗肿瘤药物的高度有效的靶点。第二类酶以依赖于ATP的机制催化一个DNA双链通过另一个双链的转移。古生菌DNA拓扑异构酶VI是一种II型酶，由于其体积小，对抗肿瘤药物敏感，是进一步了解这些酶的组织和机制的良好模型。我们给出了完整的DNA拓扑异构酶VI与人Topo II的抑制剂自由基结合的晶体结构，并与小角X射线散射测定的脱脂蛋白在溶液中的构象进行了比较。这种结构，结合收集的大量关于这些酶的实验数据，使我们能够提出一个两门DNA转移机制的结构模型。
DNA topoisomerases resolve DNA topological problems created during transcription, replication, and recombination. These ubiquitous enzymes are essential for cell viability and are highly potent targets for the development of antibacterial and antitumoral drugs. Type II enzymes catalyze the transfer of a DNA duplex through another one in an ATP-dependent mechanism. Because of its small size and sensitivity to antitumoral drugs, the archaeal DNA topoisomerase VI, a type II enzyme, is an excellent model for gaining further understanding of the organization and mechanism of these enzymes. We present the crystal structure of intact DNA topoisomerase VI bound to radicicol, an inhibitor of human topo II, and compare it to the conformation of the apo-protein as determined by small-angle X-ray scattering in solution. This structure, combined with a wealth of experimental data gathered on these enzymes, allows us to propose a structural model for the two-gate DNA transfer mechanism.