| Structural highlights
6y6d is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.2Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
STMN4_RAT Exhibits microtubule-destabilizing activity.[1] [2] [3]
Publication Abstract from PubMed
Noscapine 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 Also
References
- ↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:http://dx.doi.org/10.1074/jbc.M313693200
- ↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:http://dx.doi.org/10.1002/jnr.10234
- ↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:http://dx.doi.org/10.1038/nature02393
- ↑ Oliva MA, Prota AE, Rodríguez-Salarichs J, Bennani YL, Jiménez-Barbero J, Bargsten K, Canales Á, Steinmetz MO, Díaz JF. Structural Basis of Noscapine Activation for Tubulin Binding. J Med Chem. 2020 Aug 13;63(15):8495-8501. PMID:32657585 doi:10.1021/acs.jmedchem.0c00855
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