4fdi: Difference between revisions

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-[[Image:4fdi.png|left|200px]]
+==The molecular basis of mucopolysaccharidosis IV A==
+<StructureSection load='4fdi' size='340' side='right' caption='[[4fdi]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4fdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FDI 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=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fdj|4fdj]]</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 Homo sapiens])</td></tr>
+<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>
+<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=4fdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fdi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fdi RCSB], [http://www.ebi.ac.uk/pdbsum/4fdi PDBsum]</span></td></tr>
+</table>
+== 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.
+== Function ==
-{{STRUCTURE_4fdi|  PDB=4fdi  |  SCENE=  }}
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===The molecular basis of mucopolysaccharidosis IV A===
+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>
-{{ABSTRACT_PUBMED_22940367}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+==See Also==
-[[4fdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FDI OCA].
+*[[Caspase|Caspase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: N-acetylgalactosamine-6-sulfatase]]
-[[Category: Garman, S C.]]
+[[Category: Garman, S C]]
-[[Category: Rivera-Colon, Y.]]
+[[Category: Rivera-Colon, Y]]
 [[Category: Enzyme replacement therapy]]
 [[Category: Formylglycine]]