Rotational-Echo Double-Resonance NMR Distance Measurements for the Tubulin-Bound Paclitaxel Conformation
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- 作者：Younkee Paik ; Chao Yang ; Belhu Metaferia ; Shoubin Tang ; Susan Bane ; Rudravajhala Ravindra ; Natasha Shanker ; Ana A. Alcaraz ; Scott A. Johnson ; Jacob Schaefer ; Robert D. O'Connor ; Lynette Cegelski ; Jame
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：January 17, 2007
- 年：2007
- 卷：129
- 期：2
- 页码：361 - 370
- 全文大小：313K
- 年卷期：v.129,no.2(January 17, 2007)
- ISSN：1520-5126
文摘
The important anticancer drug Taxol (paclitaxel, PTX) owes its unique activity to its ability tobind to tubulin in a stoichiometric ratio and promote its assembly into microtubules. The conformation ofthe microtubule-bound drug has been the focus of numerous research efforts, since the inability ofpolymerized tubulin to form crystals precludes structure proof by X-ray crystallography. Likewise, althoughthe 
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ddle">-tubulin dimer structure has been solved by electron crystallography, the 3.7 Å resolution is too lowto permit direct determination of either ligand conformation or binding pose. In this article, we presentexperimental results from 2H{19F} REDOR NMR that provide direct confirmation that paclitaxel adopts aT-shaped conformation when it is bound to tubulin.
,ddle">-tubulin dimer structure has been solved by electron crystallography, the 3.7 Å resolution is too lowto permit direct determination of either ligand conformation or binding pose. In this article, we presentexperimental results from 2H{19F} REDOR NMR that provide direct confirmation that paclitaxel adopts aT-shaped conformation when it is bound to tubulin.