Rotational-echo double-resonance NMR distance measurements for the tubulin-bound paclitaxel conformation
Rotational-echo double-resonance NMR distance measurements for the tubulin-bound paclitaxel conformation
复制标题
DOI：
10.1021/ja0656604
复制
发表时间：
2007-01-17
影响因子：
15
通讯作者：
Kingston, David G. I.
中科院分区：
文献类型：
--
作者：
Paik, Younkee;Yang, Chao;Kingston, David G. I.
重要的抗癌药物紫杉醇(紫杉醇，PTX)的独特活性归功于它能够以化学计量比与微管蛋白结合，并促进其组装成微管。微管结合药物的构象一直是众多研究工作的焦点，因为聚合的微管蛋白不能形成晶体，因此无法通过X射线结晶学进行结构验证。同样，尽管电子结晶学已经解决了α，β-微管蛋白二聚体的结构，但3.7A的分辨率太低，无法直接确定配体的构象或结合姿势。在这篇文章中，我们给出了H-2{F-19}Redor核磁共振的实验结果，直接证实了紫杉醇在与微管蛋白结合时采用了T型构象。
The important anticancer drug Taxol (paclitaxel, PTX) owes its unique activity to its ability to bind to tubulin in a stoichiometric ratio and promote its assembly into microtubules. The conformation of the microtubule-bound drug has been the focus of numerous research efforts, since the inability of polymerized tubulin to form crystals precludes structure proof by X-ray crystallography. Likewise, although the alpha,beta-tubulin dimer structure has been solved by electron crystallography, the 3.7 A resolution is too low to permit direct determination of either ligand conformation or binding pose. In this article, we present experimental results from H-2{F-19} REDOR NMR that provide direct confirmation that paclitaxel adopts a T-shaped conformation when it is bound to tubulin.