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| - | [[Image:1r47.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1r47| PDB=1r47 | SCENE= }} | | {{STRUCTURE_1r47| PDB=1r47 | SCENE= }} |
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| - | '''Structure of human alpha-galactosidase'''
| + | ===Structure of human alpha-galactosidase=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15003450}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15003450 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15003450}} |
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| | ==Disease== | | ==Disease== |
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| | [[Category: Glycosidase]] | | [[Category: Glycosidase]] |
| | [[Category: Lysosomal enzyme]] | | [[Category: Lysosomal enzyme]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:03:10 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:14:54 2008'' |
Revision as of 12:14, 29 July 2008
Template:STRUCTURE 1r47
Structure of human alpha-galactosidase
Template:ABSTRACT PUBMED 15003450
Disease
Known disease associated with this structure: Fabry disease OMIM:[300644], Fabry disease, cardiac variant OMIM:[300644]
About this Structure
1R47 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The molecular defect leading to Fabry disease: structure of human alpha-galactosidase., Garman SC, Garboczi DN, J Mol Biol. 2004 Mar 19;337(2):319-35. PMID:15003450
Page seeded by OCA on Tue Jul 29 15:14:54 2008
