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DC Field	Value	Language
dc.contributor.author	Field, Jessica J.	es_ES
dc.contributor.author	Pera, Benet	es_ES
dc.contributor.author	Estévez-Gallego, Juan	es_ES
dc.contributor.author	Rodríguez-Salarichs, Javier	es_ES
dc.contributor.author	Sáez-Calvo, Gonzalo	es_ES
dc.contributor.author	Andreu, José Manuel	es_ES
dc.contributor.author	Díaz, José Fernando	es_ES
dc.date.accessioned	2017-10-18T09:03:55Z	-
dc.date.available	2017-10-18T09:03:55Z	-
dc.date.issued	2017-10-12	-
dc.identifier.citation	J. Nat. Prod., Article ASAP (2017)	es_ES
dc.identifier.issn	0163-3864	-
dc.identifier.uri	http://hdl.handle.net/10261/156392	-
dc.description	41 p.-8 fig.-2 tab. Field, Jessica J. et al.	es_ES
dc.description.abstract	The marine natural product zampanolide and analogues thereof constitute a new chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in the assembly prone form and, thus, represents an assembly activated state of the protein. In this study, we have characterized the biochemical properties of the covalently modified, activated tubulin dimer, and we have determined the effect of zampanolide on tubulin association and the binding of tubulin ligands at other binding sites. Tubulin activation by zampanolide does not affect its longitudinal oligomerization but does alter its lateral association properties. The covalent binding of zampanolide to β-tubulin affects both the colchicine site, causing a change of the quantum yield of the bound ligand, and the exchangeable nucleotide binding site, reducing the affinity for the nucleotide. While these global effects do not change the binding affinity of 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC) (a reversible binder of the colchicine site), the binding affinity of a fluorescent analogue of GTP (Mant-GTP) at the nucleotide E-site is reduced from 12 ± 2 × 105 M-1 in the case of unmodified tubulin to 1.4 ± 0.3 × 105 M-1 in the case of the zampanolide tubulin adduct, indicating signal transmission between the taxane site and the colchicine and nucleotide sites of β-tubulin.	es_ES
dc.description.sponsorship	This work was supported in part by grants BFU2016-75319-R (AEI/FEDER, UE) from Ministerio de Economia y Competitividad and the Cancer Society of New Zealand, and the Wellington Medical Research Foundation (JJF & JHM). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery”. The CNIC is supported by the Ministerio de Ciencia e Innovación and the Fundación Pro CNIC.	es_ES
dc.language.iso	eng	es_ES
dc.publisher	American Chemical Society	es_ES
dc.relation	MINECO/ICTI2013-2016/BFU2016-75319-R	es_ES
dc.relation.isversionof	Postprint	es_ES
dc.rights	openAccess	en_EN
dc.title	Zampanolide binding to tubulin indicates crosstalk of taxane site with colchicine and nucleotide sites	es_ES
dc.type	artículo	es_ES
dc.identifier.doi	10.1021/acs.jnatprod.7b00704	-
dc.description.peerreviewed	Peer reviewed	es_ES
dc.relation.publisherversion	http://dx.doi.org/10.1021/acs.jnatprod.7b00704	es_ES
dc.identifier.e-issn	1520-6025	-
dc.embargo.terms	2018-10-12	es_ES
dc.contributor.funder	Ministerio de Economía y Competitividad (España)	es_ES
dc.contributor.funder	Cancer Society of New Zealand	es_ES
dc.contributor.funder	Wellington Medical Research Foundation	es_ES
dc.relation.csic	Sí	es_ES
oprm.item.hasRevision	no ko 0 false	*
dc.identifier.funder	http://dx.doi.org/10.13039/501100001513	es_ES
dc.identifier.funder	http://dx.doi.org/10.13039/501100003329	es_ES
dc.identifier.funder	http://dx.doi.org/10.13039/501100001528	es_ES
Appears in Collections:	(CIB) Artículos