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| | ==The molecular basis of mucopolysaccharidosis IV A, complex with GalNAc== | | ==The molecular basis of mucopolysaccharidosis IV A, complex with GalNAc== |
| - | <StructureSection load='4fdj' size='340' side='right' caption='[[4fdj]], [[Resolution|resolution]] 2.81Å' scene=''> | + | <StructureSection load='4fdj' size='340' side='right'caption='[[4fdj]], [[Resolution|resolution]] 2.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fdj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fdj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FDJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DDZ:3,3-DIHYDROXY+L-ALANINE'>DDZ</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DDZ:3,3-DIHYDROXY+L-ALANINE'>DDZ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fdi|4fdi]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4fdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fdj OCA], [https://pdbe.org/4fdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fdj RCSB], [https://www.ebi.ac.uk/pdbsum/4fdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fdj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GALNS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-acetylgalactosamine-6-sulfatase N-acetylgalactosamine-6-sulfatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.6.4 3.1.6.4] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fdj OCA], [http://pdbe.org/4fdj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fdj RCSB], [http://www.ebi.ac.uk/pdbsum/4fdj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fdj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GALNS_HUMAN GALNS_HUMAN]] Mucopolysaccharidosis type 4A. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/GALNS_HUMAN GALNS_HUMAN] Mucopolysaccharidosis type 4A. The disease is caused by mutations affecting the gene represented in this entry. |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/GALNS_HUMAN GALNS_HUMAN] |
| - | Lysosomal enzymes catalyze the breakdown of macromolecules in the cell. In humans, loss of activity of a lysosomal enzyme leads to an inherited metabolic defect known as a lysosomal storage disorder. The human lysosomal enzyme galactosamine-6-sulfatase (GALNS, also known as N-acetylgalactosamine-6-sulfatase and GalN6S; E.C. 3.1.6.4) is deficient in patients with the lysosomal storage disease mucopolysaccharidosis IV A (also known as MPS IV A and Morquio A). Here, we report the three-dimensional structure of human GALNS, determined by X-ray crystallography at 2.2A resolution. The structure reveals a catalytic gem diol nucleophile derived from modification of a cysteine side chain. The active site of GALNS is a large, positively charged trench suitable for binding polyanionic substrates such as keratan sulfate and chondroitin-6-sulfate. Enzymatic assays on the insect-cell-expressed human GALNS indicate activity against synthetic substrates and inhibition by both substrate and product. Mapping 120 MPS IV A missense mutations onto the structure reveals that a majority of mutations affect the hydrophobic core of the structure, indicating that most MPS IV A cases result from misfolding of GALNS. Comparison of the structure of GALNS to paralogous sulfatases shows a wide variety of active-site geometries in the family but strict conservation of the catalytic machinery. Overall, the structure and the known mutations establish the molecular basis for MPS IV A and for the larger MPS family of diseases.
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| - | | + | |
| - | The Structure of Human GALNS Reveals the Molecular Basis for Mucopolysaccharidosis IV A.,Rivera-Colon Y, Schutsky EK, Kita AZ, Garman SC J Mol Biol. 2012 Aug 29. PMID:22940367<ref>PMID:22940367</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4fdj" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Sulfatase|Sulfatase]] | + | *[[Sulfatase 3D structures|Sulfatase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: N-acetylgalactosamine-6-sulfatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Garman, S C]] | + | [[Category: Garman SC]] |
| - | [[Category: Rivera-Colon, Y]] | + | [[Category: Rivera-Colon Y]] |
| - | [[Category: Carbohydrate-binding protein]]
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| - | [[Category: Enzyme replacement therapy]]
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| - | [[Category: Formylglycine]]
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| - | [[Category: Glycoprotein]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Lysosomal enzyme]]
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| - | [[Category: N-linked glycosylation]]
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| - | [[Category: Sulfatase]]
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