6y6d
From Proteopedia
Jump to navigationJump to search
Structural highlights
FunctionSTMN4_RAT Exhibits microtubule-destabilizing activity.[1] [2] [3] Publication Abstract from PubMedNoscapine is a natural alkaloid that is used as an antitussive medicine. However, it also acts as a weak anticancer agent in certain in vivo models through a mechanism that is largely unknown. Here, we performed structural studies and show that the cytotoxic agent 7A-O-demethoxy-amino-noscapine (7A-aminonoscapine) binds to the colchicine site of tubulin. We suggest that the 7A-methoxy group of noscapine prevents binding to tubulin due to a steric clash of the compound with the T5-loop of alpha-tubulin. We further propose that the anticancer activity of noscapine arises from a bioactive metabolite that binds to the colchicine site of tubulin to induce mitotic arrest through a microtubule cytoskeleton-based mechanism. Structural basis of noscapine activation for tubulin binding.,Oliva MA, Prota AE, Rodriguez-Salarichs J, Gu W, Bennani YL, Jimenez-Barbero J, Bargsten K, Canales A, Steinmetz MO, Diaz JF J Med Chem. 2020 Jul 13. doi: 10.1021/acs.jmedchem.0c00855. PMID:32657585[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
This page was last modified 13:20, 24 January 2024.