View source for 4fdj


==The molecular basis of mucopolysaccharidosis IV A, complex with GalNAc==
<StructureSection load='4fdj' size='340' side='right'caption='[[4fdj]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81&#8491;</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='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>
</table>
== Disease ==
[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.
== Function ==
[https://www.uniprot.org/uniprot/GALNS_HUMAN GALNS_HUMAN] 
<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 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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fdj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sulfatase 3D structures|Sulfatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Garman SC]]
[[Category: Rivera-Colon Y]]