Structural basis of swinholide a binding to actin
Structural basis of swinholide a binding to actin
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DOI：
10.1016/j.chembiol.2005.02.011
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发表时间：
2005-03-01
影响因子：
--
通讯作者：
Rayment, I
中科院分区：
文献类型：
--
作者：
Klenchin, VA;King, R;Rayment, I
针对肌动蛋白细胞骨架的海洋毒素代表了一类新的和有前途的抗癌化合物。在这里，我们提出了一个2.0埃的分辨率结构swinholide A，海洋大环内酯，绑定到两个肌动蛋白分子。结构表明，肌动蛋白二聚体的复合物并不代表生理相关的实体，两个肌动蛋白分子不相互作用。swinholide A肌动蛋白结合位点与trisoxazole家族毒素和许多肌动蛋白结合蛋白的靶向位点相同，突出了该位点在肌动蛋白聚合中的重要性。所观察到的结构揭示了swinholide A的作用机制，并提供了一个结构框架，围绕该框架设计针对细胞骨架的新药物。
Marine toxins targeting the actin cytoskeleton represent a new and promising class of anti-cancer compounds. Here we present a 2.0 angstrom resolution structure of swinholide A, a marine macrolide, bound to two actin molecules. The structure demonstrates that the actin dimer in the complex does not represent a physiologically relevant entity, for the two actin molecules do not interact with each other. The swinholide A actin binding site is the same as that targeted by toxins of the trisoxazole family and numerous actin binding proteins, highlighting the importance of this site in actin polymerization. The observed structure reveals the mechanism of action of swinholide A and provides a structural framework about which to design new agents directed at the cytoskeleton.