Allingham J S, Klenchin V A, Rayment I
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, Wisconsin 53706, USA.
Cell Mol Life Sci. 2006 Sep;63(18):2119-34. doi: 10.1007/s00018-006-6157-9.
Natural small-molecule inhibitors of actin cytoskeleton dynamics have long been recognized as valuable molecular probes for dissecting complex mechanisms of cellular function. More recently, their potential use as chemotherapeutic drugs has become a focus of scientific investigation. The primary focus of this review is the molecular mechanism by which different actin-targeting natural products function, with an emphasis on structural considerations of toxins for which high-resolution structural information of their interaction with actin is available. By comparing the molecular interactions made by different toxin families with actin, the structural themes of those that alter filament dynamics in similar ways can be understood. This provides a framework for novel synthetic-compound designs with tailored functional properties that could be applied in both research and clinical settings.
肌动蛋白细胞骨架动力学的天然小分子抑制剂长期以来一直被认为是剖析细胞功能复杂机制的有价值的分子探针。最近，它们作为化疗药物的潜在用途已成为科学研究的焦点。本综述的主要重点是不同靶向肌动蛋白的天然产物发挥作用的分子机制，重点是那些可获得其与肌动蛋白相互作用的高分辨率结构信息的毒素的结构考量。通过比较不同毒素家族与肌动蛋白的分子相互作用，可以理解那些以相似方式改变细丝动力学的毒素的结构主题。这为具有定制功能特性的新型合成化合物设计提供了一个框架，可应用于研究和临床环境。
