5O7A

Quinolin-6-yloxyacetamides are microtubule destabilizing agents that bind to the colchicine site of tubulin

5O7A の概要

• エントリーDOI: 10.2210/pdb5o7a/pdb
• 分子名称: Tubulin alpha-1B chain, Tubulin beta-2B chain, Stathmin-4, ... (10 entities in total)
• 機能のキーワード: microtubules, tubulin, colchicine, quinolin-6-yloxyacetamides, motor protein
• 由来する生物種: Rattus norvegicus (Norway Rat); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 264877.29

構造登録者

Sharma, A.,Olieric, N.,Steinmetz, M.O. (登録日: 2017-06-08, 公開日: 2017-07-05, 最終更新日: 2024-05-08)

主引用文献

Sharma, A.,Saez-Calvo, G.,Olieric, N.,de Asis Balaguer, F.,Barasoain, I.,Lamberth, C.,Diaz, J.F.,Steinmetz, M.O.
Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin.
Int J Mol Sci, 18:-, 2017

PubMed Abstract: Quinolin-6-yloxyacetamides (QAs) are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole. Together, our data establish QAs as colchicine-site ligands and explain the molecular mechanism of microtubule destabilization by this class of compounds. They further extend our structural knowledge on antitubulin agents and thus should aid in the development of new strategies for the rational design of ligands against multidrug-resistant cancer cells.

PubMed: 28640209
DOI: 10.3390/ijms18071336

実験手法

X-RAY DIFFRACTION (2.495 Å)