Structural highlights
8wd0 is a 6 chain structure with sequence from Bos taurus, Gallus gallus, Rattus norvegicus and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.6Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TBA1B_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Publication Abstract from PubMed
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 beta-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 beta-tubulin, inhibited tubulin polymerization, and displayed anticancer activity against paclitaxel-resistant cells, offering valuable insights for further exploration as potential anticancer agents.
The cytotoxic natural compound erianin binds to colchicine site of beta-tubulin and overcomes taxane resistance.,Yan W, Zhou Y, Yuan X, Bai P, Tang M, Chen L, Wei H, Yang J Bioorg Chem. 2024 Jun 17;150:107569. doi: 10.1016/j.bioorg.2024.107569. PMID:38905886[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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 β-tubulin and overcomes taxane resistance. Bioorg Chem. 2024 Jun 17;150:107569. PMID:38905886 doi:10.1016/j.bioorg.2024.107569
