Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/135534
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Pironetin binds covalently to Cys316 and perturbs a major loop and helix of -tubulin to inhibit microtubule formation |
Autor: | Prota, Andrea E.; Setter, J.; Waight, Andrew B.; Bargsten, Katja; Murga, Juan; Díaz, José Fernando CSIC ORCID ; Steinmetz, Michel O. | Palabras clave: | Anticancer drugs Microtubule-targeting agents Molecular mechanism of action Protein–ligand interactions X-ray crystallography |
Fecha de publicación: | 31-jul-2016 | Editor: | Elsevier | Citación: | Journal of Molecular Biology 428 (15) 2981-2988 (2016) | Resumen: | Microtubule-targeting agents are among the most powerful drugs used in chemotherapy to treat cancer patients. Pironetin is a natural product that displays promising anticancer properties by binding to and potently inhibiting tubulin assembly into microtubules; however, its molecular mechanism of action remained obscure. Here, we solved the crystal structure of the tubulin–pironetin complex and found that the compound covalently binds to Cys316 of α-tubulin. The structure further revealed that pironetin perturbs the T7 loop and helix H8 of α-tubulin. Since both these elements are essential for establishing longitudinal tubulin contacts in microtubules, this result explains how pironetin inhibits the formation of microtubules. Together, our data define the molecular details of the pironetin binding site on α-tubulin and thus offer a promising basis for the rational design of pironetin variants with improved activity profiles. They further extend our knowledge on strategies evolved by natural products to target and perturb the microtubule cytoskeleton. | Descripción: | 21 p.-4 fig.-1 tab. | Versión del editor: | http://dx.doi.org/ 10.1016/j.jmb.2016.06.023 | URI: | http://hdl.handle.net/10261/135534 | DOI: | 10.1016/j.jmb.2016.06.023 | ISSN: | 0022-2836 | E-ISSN: | 1089-8638 |
Aparece en las colecciones: | (CIB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
JMB-D-16-.pdf | Postprint | 975,77 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
64
checked on 15-mar-2024
WEB OF SCIENCETM
Citations
59
checked on 25-feb-2024
Page view(s)
250
checked on 18-mar-2024
Download(s)
324
checked on 18-mar-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.