6JCJ

Structure of crolibulin in complex with tubulin

6JCJ の概要

• エントリーDOI: 10.2210/pdb6jcj/pdb
• 分子名称: Tubulin alpha-1B chain, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, Tubulin beta-2B chain, ... (11 entities in total)
• 機能のキーワード: cbsis, colchicine binding site inhibitors, cell cycle
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 264810.51

構造登録者

Zhang, Z.,Yang, J. (登録日: 2019-01-29, 公開日: 2019-03-13, 最終更新日: 2023-11-22)

主引用文献

Zhang, Z.,Wang, C.,Ma, L.,Jiang, X.,Wu, C.,Wang, Y.,Jiang, Y.,Zheng, W.,Yang, Y.,Ma, Y.,Yang, J.
Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.
Biochem. Biophys. Res. Commun., 511:381-386, 2019

PubMed Abstract: Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5 Å crystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs.

PubMed: 30803758
DOI: 10.1016/j.bbrc.2019.02.064

実験手法

X-RAY DIFFRACTION (2.5 Å)