Kamel Karol, Kolinski Andrzej
Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Warszawa, Poland.
Acta Biochim Pol. 2011;58(2):255-60. Epub 2011 Jun 2.
Understanding the interactions of epothilones with β-tubulin is crucial for computer aided rational design of macrocyclic drugs based on epothilones and epothilone derivatives. Despite numerous structure-activity relationship investigations we still lack substantial knowledge about the binding mode of epothilones and their derivatives to β-tubulin. In this work, we reevaluated the electron crystallography structure of epothilone A/β-tubulin complex (PDB entry 1TVK) and proposed an alternative binding mode of epothilone A to β-tubulin that explains more experimental facts.
了解埃坡霉素与β-微管蛋白的相互作用对于基于埃坡霉素及其衍生物的大环药物的计算机辅助合理设计至关重要。尽管进行了大量的构效关系研究，但我们仍然缺乏关于埃坡霉素及其衍生物与β-微管蛋白结合模式的实质性知识。在这项工作中，我们重新评估了埃坡霉素A/β-微管蛋白复合物的电子晶体学结构（PDB条目1TVK），并提出了埃坡霉素A与β-微管蛋白的另一种结合模式，该模式解释了更多的实验事实。
