English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/51625
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
Exportar a otros formatos:
Title

Insights into the interaction of discodermolide and docetaxel with tubulin. Mapping the binding sites of microtubule-stabilizing agents by using an integrated NMR and computational approach

AuthorsCanales, Ángeles ; Rodríguez-Salarichs, Javier; Trigili, Chiara ; Nieto, Lidia ; Coderch, Claire; Andreu, José Manuel ; Paterson, Ian; Jiménez-Barbero, Jesús ; Díaz, José Fernando
Issue Date19-Aug-2011
PublisherAmerican Chemical Society
CitationACS Chemical Biology 6(8):789-799(2011)
AbstractThe binding interactions of two antitumor agents that target the paclitaxel site, docetaxel and discodermolide, to unassembled α/β-tubulin heterodimers and microtubules have been studied using biochemical and NMR techniques. The use of discodermolide as a water-soluble paclitaxel biomimetic and extensive NMR experiments allowed the detection of binding of microtubule-stabilizing agents to unassembled tubulin α/β-heterodimers. The bioactive 3D structures of docetaxel and discodermolide bound to α/β-heterodimers were elucidated and compared to those bound to microtubules, where subtle changes in the conformations of docetaxel in its different bound states were evident. Moreover, the combination of experimental TR-NOE and STD NMR data with CORCEMA-ST calculations indicate that docetaxel and discodermolide target an additional binding site at the pore of the microtubules, which is different from the internal binding site at the lumen previously determined by electron crystallography. Binding to this pore site can then be considered as the first ligand-protein recognition event that takes place in advance of the drug internalization process and interaction with the lumen of the microtubules
Description41 p.-7 fig.-3 fig.-supl.
Publisher version (URL)http://dx.doi.org/10.1021/cb200099u
URIhttp://hdl.handle.net/10261/51625
DOI10.1021/cb200099u
ISSN1554-8929
E-ISSN1554-8937
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
2011 Canales_et_al.pdf953,84 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.