6Y6D
Tubulin-7-Aminonoscapine complex
Summary for 6Y6D
| Entry DOI | 10.2210/pdb6y6d/pdb |
| Descriptor | Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, GLYCEROL, ... (13 entities in total) |
| Functional Keywords | cell cycle, tubulin fold, cytoskeleton, microtubule |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 6 |
| Total formula weight | 265355.12 |
| Authors | Oliva, M.A.,Prota, A.E.,Rodriguez-Salarichs, J.,Gu, W.,Bennani, Y.L.,Jimenez-Barbero, J.,Canales, A.,Steinmetz, M.O.,Diaz, J.F. (deposition date: 2020-02-26, release date: 2020-07-22, Last modification date: 2024-01-24) |
| Primary citation | Oliva, M.A.,Prota, A.E.,Rodriguez-Salarichs, J.,Bennani, Y.L.,Jimenez-Barbero, J.,Bargsten, K.,Canales, A.,Steinmetz, M.O.,Diaz, J.F. Structural Basis of Noscapine Activation for Tubulin Binding. J.Med.Chem., 63:8495-8501, 2020 Cited by PubMed Abstract: Noscapine is a natural alkaloid that is used as an antitussive medicine. However, it also acts as a weak anticancer agent in certain models through a mechanism that is largely unknown. Here, we performed structural studies and show that the cytotoxic agent 7A--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 α-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. PubMed: 32657585DOI: 10.1021/acs.jmedchem.0c00855 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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