期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：9
页码：5312-5316
DOI：10.1073/pnas.051309398
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The chemotherapeutic drug Taxol is known to interact within a specific site on {beta}-tubulin. Although the general location of the site has been defined by photoaffinity labeling and electron crystallography, the original data were insufficient to make an absolute determination of the bound conformation. We have now correlated the crystallographic density with analysis of Taxol conformations and have found the unique solution to be a T-shaped Taxol structure. This T-shaped or butterfly structure is optimized within the {beta}-tubulin site and exhibits functional similarity to a portion of the B9-B10 loop in the -tubulin subunit. The model provides structural rationalization for a sizeable body of Taxol structure-activity relationship data, including binding affinity, photoaffinity labeling, and acquired mutation in human cancer cells.
