8WD0

Crystal structure of T2R-TTL-Erianin complex

Summary for 8WD0

• Entry DOI: 10.2210/pdb8wd0/pdb
• Descriptor: Tubulin alpha-1B chain, 2-methoxy-5-[2-(3,4,5-trimethoxyphenyl)ethyl]phenol, GUANOSINE-5'-DIPHOSPHATE, ... (13 entities in total)
• Functional Keywords: microtubule, cell cycle
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 269979.26

Authors

Yang, J. (deposition date: 2023-09-14, release date: 2024-07-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)