English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/77558
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites

AuthorsBuey, Ruben M.; Calvo, Enrique; Barasoain, Isabel ; Pineda, Oriol; Edler, Michael C.; Matesanz, Ruth ; Cerezo, Gemma; Vanderwal, Christopher D.; Day, Billy W.; Sorensen, Erik J.; López, Juan Antonio; Andreu, José Manuel ; Hamel, Ernest; Díaz, José Fernando
Issue DateJan-2007
PublisherNature Publishing Group
CitationNature Chemical Biology 3:117-125(2007)
AbstractCyclostreptin (1), a natural product from Streptomyces sp. 9885, irreversibly stabilizes cellular microtubules, causes cell cycle arrest, evades drug resistance mediated by P-glycoprotein in a tumor cell line and potently inhibits paclitaxel binding to microtubules, yet it only weakly induces tubulin assembly. In trying to understand this paradox, we observed irreversible binding of synthetic cyclostreptin to tubulin. This results from formation of covalent crosslinks to β-tubulin in cellular microtubules and microtubules formed from purified tubulin in a 1:1 total stoichiometry distributed between Thr220 (at the outer surface of a pore in the microtubule wall) and Asn228 (at the lumenal paclitaxel site). Unpolymerized tubulin was only labeled at Thr220. Thus, the pore region of β-tubulin is an undescribed binding site that (i) elucidates the mechanism by which taxoid-site compounds reach the kinetically unfavorable lumenal site and (ii) explains how taxoid-site drugs induce microtubule formation from dimeric and oligomeric tubulin. © 2007 Nature Publishing Group.
Publisher version (URL)http://dx.doi.org/10.1038/nchembio853
URIhttp://hdl.handle.net/10261/77558
DOI10.1038/nchembio853
Identifiersdoi: 10.1038/nchembio853
issn: 1552-4450
e-issn: 1552-4469
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
cyclostreptin_Buey.pdf538,8 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.