| http://purl.uniprot.org/citations/15003450 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15003450 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15003450 | http://www.w3.org/2000/01/rdf-schema#comment | "Fabry disease is an X-linked lysosomal storage disease afflicting 1 in 40,000 males with chronic pain, vascular degeneration, cardiac impairment, and other symptoms. Deficiency in the lysosomal enzyme alpha-galactosidase (alpha-GAL) causes an accumulation of its substrate, which ultimately leads to Fabry disease symptoms. Here, we present the structure of the human alpha-GAL glycoprotein determined by X-ray crystallography. The structure is a homodimer with each monomer containing a (beta/alpha)8 domain with the active site and an antiparallel beta domain. N-linked carbohydrate appears at six sites in the glycoprotein dimer, revealing the basis for lysosomal transport via the mannose-6-phosphate receptor. To understand how the enzyme cleaves galactose from glycoproteins and glycolipids, we also determined the structure of the complex of alpha-GAL with its catalytic product. The catalytic mechanism of the enzyme is revealed by the location of two aspartic acid residues (D170 and D231), which act as a nucleophile and an acid/base, respectively. As a point mutation in alpha-GAL can lead to Fabry disease, we have catalogued and plotted the locations of 245 missense and nonsense mutations in the three-dimensional structure. The structure of human alpha-GAL brings Fabry disease into the realm of molecular diseases, where insights into the structural basis of the disease phenotypes might help guide the clinical treatment of patients."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2004.01.035"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2004.01.035"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/author | "Garboczi D.N."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/author | "Garboczi D.N."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/author | "Garman S.C."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/author | "Garman S.C."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/pages | "319-335"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/pages | "319-335"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/title | "The molecular defect leading to Fabry disease: structure of human alpha-galactosidase."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/title | "The molecular defect leading to Fabry disease: structure of human alpha-galactosidase."xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/volume | "337"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://purl.uniprot.org/core/volume | "337"xsd:string |
| http://purl.uniprot.org/citations/15003450 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15003450 |
| http://purl.uniprot.org/citations/15003450 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15003450 |
| http://purl.uniprot.org/citations/15003450 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15003450 |
| http://purl.uniprot.org/citations/15003450 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15003450 |
| http://purl.uniprot.org/uniprot/P06280 | http://purl.uniprot.org/core/citation | http://purl.uniprot.org/citations/15003450 |
| http://purl.uniprot.org/uniprot/P06280#attribution-9FB41DFB002E2F88AFD9C69F1D87BE51 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/15003450 |