Mostrar el registro sencillo del ítem
Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease
dc.contributor.author | Citro, Valentina | |
dc.contributor.author | Den Haan, Helena | |
dc.contributor.author | Del Prete, Rosita | |
dc.contributor.author | Liguori, Ludovica | |
dc.contributor.author | Cimmaruta, Chiara | |
dc.contributor.author | Lukas, Jan | |
dc.contributor.author | Cubellis, Maria Vittoria | |
dc.contributor.author | Andreotti, Giuseppina | |
dc.contributor.author | Pérez Sánchez, Horacio | |
dc.contributor.author | Peña García, Jorge | |
dc.date.accessioned | 2017-05-24T13:18:43Z | |
dc.date.available | 2017-05-24T13:18:43Z | |
dc.date.issued | 2016-10-27 | |
dc.identifier.uri | http://hdl.handle.net/10952/2318 | |
dc.description.abstract | Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. | es |
dc.description.sponsorship | Funding was provided by Telethon - Italy (Grant no. GGP12108). This work was partially supported by the Fundación Séneca del Centro de Coordinación de la Investigación de la Región de Murcia under Project 18946/JLI/13. Powered@NLHPC: This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM-02). | es |
dc.language.iso | en | es |
dc.rights | Attribution-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nd/4.0/ | * |
dc.subject | Fabry | es |
dc.subject | Drug discovery | es |
dc.subject | High Performance Computing | es |
dc.subject | Computational Chemistry | es |
dc.title | Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease | es |
dc.type | article | es |
dc.rights.accessRights | openAccess | es |
dc.journal.title | PLOS ONE | es |
dc.description.discipline | Farmacia | es |
dc.description.discipline | Medicina | es |