6KPP

BNC105 in complex with tubulin

6KPP の概要

• エントリーDOI: 10.2210/pdb6kpp/pdb
• 分子名称: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, GLYCEROL, ... (12 entities in total)
• 機能のキーワード: bnc105, tubulin, protein-drug complex, antitumor protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 264734.52

構造登録者

Wang, T.,Wu, C.,Pu, D. (登録日: 2019-08-15, 公開日: 2020-08-19, 最終更新日: 2023-11-22)

主引用文献

Wang, T.,Wu, C.,Wang, C.,Zhang, G.,Arnst, K.E.,Yao, Y.,Zhang, Z.,Wang, Y.,Pu, D.,Li, W.
Unraveling the molecular mechanism of BNC105, a phase II clinical trial vascular disrupting agent, provides insights into drug design.
Biochem.Biophys.Res.Commun., 2020

PubMed Abstract: Microtubules are made up of tubulin protein and play a very important part in numerous cellular events of eukaryotic cells, which is why they are seen as attractive targets for tumor chemotherapy. BNC105, a known vascular targeting agent, has entered in phase II clinical trials. It has previously been confirmed that BNC105 is an effective microtubule targeting agent for various cancers. BNC105 exhibits selectivity for tumor cells, elicits vascular disrupting effects, and inhibits tumor growth. However, the molecular mechanism of BNC105 is still elusive. Herein, the crystal structure of BNC105 in complex with tubulin protein is revealed, demonstrating the its interaction with the colchicine binding site. In order to thoroughly evaluate its molecular mechanism from a structural-activity-relationship standpoint, the binding mode of tubulin to BNC-105 is compared with colchicine, CA-4 and other BNC-105 derivatives. Our study not only confirms the detailed interactions of the BNC105-tubulin complex, but also offer substantial structural foundation for the design and development of novel benzo[b]furan derivatives as microtubule targeting agents.

PubMed: 32085900
DOI: 10.1016/j.bbrc.2019.12.083

実験手法

X-RAY DIFFRACTION (2.74524106157 Å)