2026-07-21T13:51:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/75552024-09-27T10:16:27Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19607
Repisalud
author
Field, Jessica J
author
Pera, Benet
author
Calvo, Enrique
author
Canales, Angeles
author
Zurwerra, Didier
author
Trigili, Chiara
author
Rodríguez-Salarichs, Javier
author
Matesanz, Ruth
author
Kanakkanthara, Arun
author
Wakefield, St John
author
Singh, A Jonathan
author
Jiménez-Barbero, Jesús
author
Northcote, Peter
author
Miller, John H
author
Lopez, Juan Antonio
author
Hamel, Ernest
author
Barasoain, Isabel
author
Altmann, Karl-Heinz
author
Díaz, José Fernando
funder
Minsterio de Ciencia, Tecnología y Medio Ambiente (Cuba)
funder
European Molecular Biology Organization
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Cancer Society of New Zealand
funder
Wellington Medical Research Foundation
funder
Fundación ProCNIC
2019-05-09T07:25:51Z
2019-05-09T07:25:51Z
2012-06-22
Chem Biol. 2012; 19(6):686-98
10.1016/j.chembiol.2012.05.008
1879-1301
10745521
Chemistry & biology
22726683
http://hdl.handle.net/20.500.12105/7555
Zampanolide and its less active analog dactylolide compete with paclitaxel for binding to microtubules and represent a new class of microtubule-stabilizing agent (MSA). Mass spectrometry demonstrated that the mechanism of action of both compounds involved covalent binding to β-tubulin at residues N228 and H229 in the taxane site of the microtubule. Alkylation of N228 and H229 was also detected in α,β-tubulin dimers. However, unlike cyclostreptin, the other known MSA that alkylates β-tubulin, zampanolide was a strong MSA. Modeling the structure of the adducts, using the NMR-derived dactylolide conformation, indicated that the stabilizing activity of zampanolide is likely due to interactions with the M-loop. Our results strongly support the existence of the luminal taxane site of microtubules in tubulin dimers and suggest that microtubule nucleation induction by MSAs may proceed through an allosteric mechanism.
eng
Zampanolide, a potent new microtubule-stabilizing agent, covalently reacts with the taxane luminal site in tubulin α,β-heterodimers and microtubules
journal article
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URL
https://repisalud.isciii.es/bitstreams/c3b6c747-668b-436d-9dea-d1f2c82fc2fd/download
File
MD5
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application/pdf
ZampanolidePotentNewMicrotubule_2012.pdf
URL
https://repisalud.isciii.es/bitstreams/8ac38fd9-e08d-4f3d-ba61-cca7438129eb/download
File
MD5
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text/plain
ZampanolidePotentNewMicrotubule_2012.pdf.txt