Probing the Pore Drug Binding Site of Microtubules with Fluorescent Taxanes: Evidence of Two Binding Poses

被引：20

作者：

Barasoain, Isabel ^{[1
]}

Garcia-Carril, Ana M. ^{[1
]}

Matesanz, Ruth ^{[1
]}

Maccari, Giorgio ^{[2
]}

Trigili, Chiara ^{[1
]}

Mori, Mattia ^{[2
]}

Shi, Jing-Zhe ^{[3
]}

Fang, Wei-Shuo ^{[3
]}

Andreu, Jose M. ^{[1
]}

Botta, Maurizio ^{[2
]}

Diaz, J. Fernando ^{[1
]}

机构：

[1] CSIC, Ctr Invest Biol, E-28040 Madrid, Spain

[2] Univ Siena, Fac Pharm, Dept Pharmaceut & Chem Technol, I-53100 Siena, Italy

[3] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China

来源：

CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 03期

关键词：

BETA-TUBULIN; STABILIZING AGENTS; TAXOID SITE; PACLITAXEL; PROTEINS; THERMODYNAMICS; CONFORMATION; EQUILIBRIUM; RESISTANT; PEPTIDES;

D O I：

10.1016/j.chembiol.2010.02.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The pore site in microtubules has been studied with the use of Hexaflutax, a fluorescent probe derived from paclitaxel. The compound is active in cells with similar effects to paclitaxel, indicating that the pore may be a target to microtubule stabilizing agents. While other taxanes bind microtubules in a monophasic way, thus indicating a single type of sites, Hexaflutax association is biphasic. Analysis of the phases indicates that two different binding sites are detected, reflecting two different modes of binding, which could arise from different arrangements of the taxane or fluorescein moieties in the pore. Association of the 4-4-20 antifluorescein monoclonal antibody-Hexaflutax complex to microtubules remains biphasic, thus indicating that the two phases observed arise from two different poses of the taxane moiety.

引用

页码：243 / 253

页数：11

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