| http://purl.uniprot.org/citations/24737316 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24737316 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24737316 | http://www.w3.org/2000/01/rdf-schema#comment | "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-Gal(WT) and two representative mutations in GM1 gangliosidosis Japanese patients, β-Gal(R201C) and β-Gal(I51T). 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 the PC potential 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."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.529529"xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.529529"xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Suzuki Y."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Suzuki Y."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Shimizu T."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Shimizu T."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Suzuki H."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Suzuki H."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Nanba E."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Nanba E."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Ohto U."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Ohto U."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Aguilar-Moncayo M."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Aguilar-Moncayo M."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Garcia Fernandez J.M."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Garcia Fernandez J.M."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Higaki K."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Higaki K."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Mena-Barragan T."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Mena-Barragan T."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Ortiz Mellet C."xsd:string |
| http://purl.uniprot.org/citations/24737316 | http://purl.uniprot.org/core/author | "Ortiz Mellet C."xsd:string |