7CNN

vinorelbine in complex with tubulin

7CNN の概要

• エントリーDOI: 10.2210/pdb7cnn/pdb
• 分子名称: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, Vinorelbine, ... (12 entities in total)
• 機能のキーワード: vincristinve, tubulin, protein-drug complex, cell cycle
• 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: 265130.76

構造登録者

Wang, Y.X.,Wu, C.Y. (登録日: 2020-08-02, 公開日: 2021-08-04, 最終更新日: 2023-11-29)

主引用文献

Chengyong, W.,Jinghong, X.,Yanyan, W.,Qing-Jie, X.,Lingling, M.,Yuyan, L.,Hai, C.,Qian, L.,Quan, Z.,Bo, S.,Yuxi, W.
The high-resolution X-ray structure of vinca-domain inhibitors of microtubules provides a rational approach for drug design.
Febs Lett., 595:195-205, 2021

PubMed Abstract: Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance and toxicities, development of novel vinca-domain ligands is still needed. In this study, we determined the high-resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5 Å. Additionally, we recapitulated all previously published high-resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca-domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt-bridge and H-bond interactions with Asp179 and Asn329 . Our studies provided the structural basis for designing novel tubulin vinca-domain ligands.

PubMed: 33220079
DOI: 10.1002/1873-3468.14003

実験手法

X-RAY DIFFRACTION (2.5 Å)