8WD0

Crystal structure of T2R-TTL-Erianin complex

8WD0 の概要

• エントリーDOI: 10.2210/pdb8wd0/pdb
• 分子名称: Tubulin alpha-1B chain, 2-methoxy-5-[2-(3,4,5-trimethoxyphenyl)ethyl]phenol, GUANOSINE-5'-DIPHOSPHATE, ... (13 entities in total)
• 機能のキーワード: microtubule, cell cycle
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 269979.26

構造登録者

Yang, J. (登録日: 2023-09-14, 公開日: 2024-07-03)

主引用文献

Yan, W.,Zhou, Y.,Yuan, X.,Bai, P.,Tang, M.,Chen, L.,Wei, H.,Yang, J.
The cytotoxic natural compound erianin binds to colchicine site of beta-tubulin and overcomes taxane resistance
Bioorg.Chem., 150:107569-, 2024

PubMed Abstract: Erianin, a natural compound derived from Dendrobium, has shown significant anticancer properties against a wide range of cancer cells. Despite the identification of multiple mechanisms of action for erianin, none of these mechanisms fully account for its broad-spectrum effect. In this study, we aimed to identify the cellular target and underlying mechanism responsible for the broad-spectrum antitumor effects of erianin. We found that erianin effectively inhibited tubulin polymerization in cancer cells and purified tubulin. Through competition binding assays and X-ray crystallography, it was revealed that erianin bound to the colchicine site of β-tubulin. Importantly, the X-ray crystal structure of the tubulin-erianin complex was solved, providing clear insight into the orientation and position of erianin in the colchicine-binding site. Erianin showed activity against paclitaxel-resistant cells, evidenced by G2/M cell cycle arrest, apoptosis-related PARP and Caspase-3 cleavage, and in vivo xenograft studies. The study concluded that erianin bound reversibly to the colchicine site of β-tubulin, inhibited tubulin polymerization, and displayed anticancer activity against paclitaxel-resistant cells, offering valuable insights for further exploration as potential anticancer agents.

PubMed: 38905886
DOI: 10.1016/j.bioorg.2024.107569

実験手法

X-RAY DIFFRACTION (2.6 Å)