dc.creator | Suzuki, Hironori | es |
dc.creator | Ohto, Umeharu | es |
dc.creator | Higaki, Katsumi | es |
dc.creator | Mena Barragán, Teresa | es |
dc.creator | Aguilar Moncayo, Matilde | es |
dc.creator | Ortiz Mellet, Carmen | es |
dc.creator | Nanba, Eiji | es |
dc.creator | García Fernández, José Manuel | es |
dc.creator | Suzuki, Yoshiyuki | es |
dc.creator | Shimizu, Toshiyuki | es |
dc.date.accessioned | 2022-02-07T18:49:34Z | |
dc.date.available | 2022-02-07T18:49:34Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Suzuki, H., Ohto, U., Higaki, K., Mena Barragán, T., Aguilar Moncayo, M., Ortiz Mellet, C.,...,Shimizu, T. (2014). Structural basis of pharmacological chaperoning for human β-galactosidase. Journal of Biological Chemistry, 289 (21), 14560-14568. | |
dc.identifier.issn | 0021-9258 | es |
dc.identifier.issn | 1083-351X | es |
dc.identifier.uri | https://hdl.handle.net/11441/129725 | |
dc.description.abstract | GM1 gangliosidosis and Morquio B disease are autosomal recessive diseases caused by the defect in the lysosomal β-galactosidase ( β-Gal), frequently related to misfolding and subsequent endoplasmic reticulum-associated degradation. Pharmacological chaperone (PC) therapy is a newly developed molecular therapeutic approach by using small molecule ligands of the mutant enzyme that are able to promote the correct folding and prevent endoplasmic reticulum-associated degradation and promote trafficking to the lysosome. In this report, we describe the enzymological properties of purified recombinant human β-GalWT and two representative mutations in GM1 gangliosidosis Japanese patients, β-GalR201C and β-GalI51T. We have also evaluated the PC effect of two competitive inhibitors of β-Gal. Moreover, we provide a detailed atomic view of the recognition mechanism of these compounds in comparison with two structurally related analogues. All compounds bind to the active site of β-Gal with the sugar-mimicking moiety making hydrogen bonds to active site residues. Moreover, the binding affinity, the enzyme selectivity, and thePCpotential are strongly affected by the mono- or bicyclic structure of the core as well as the orientation, nature, and length of the exocyclic substituent. These results provide understanding on the mechanism of action of β-Gal selective chaperoning by newly developed PC compounds. | es |
dc.description.sponsorship | Ministry of Education, Culture, Science, Sports, and Technology of Japan 13680918, 14207106 | es |
dc.description.sponsorship | Ministry of Health, Labor and Welfare of Japan H20-Kokoro-022, H22-Nanji-Ippan-002 | es |
dc.description.sponsorship | Japan Science and Technology Agency AS232Z00009G | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad SAF2010-15670, CTQ2010-15848 | es |
dc.format | application/pdf | es |
dc.format.extent | 9 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Journal of Biological Chemistry, 289 (21), 14560-14568. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Structural basis of pharmacological chaperoning for human β-galactosidase | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | 13680918 | es |
dc.relation.projectID | 14207106 | es |
dc.relation.projectID | H20-Kokoro-022 | es |
dc.relation.projectID | H22-Nanji-Ippan-002 | es |
dc.relation.projectID | AS232Z00009G | es |
dc.relation.projectID | SAF2010-15670 | es |
dc.relation.projectID | CTQ2010-15848 | es |
dc.relation.publisherversion | https://doi.org/10.1074/jbc.M113.529529 | es |
dc.identifier.doi | 10.1074/jbc.M113.529529 | es |
dc.journaltitle | Journal of Biological Chemistry | es |
dc.publication.volumen | 289 | es |
dc.publication.issue | 21 | es |
dc.publication.initialPage | 14560 | es |
dc.publication.endPage | 14568 | es |