View source for 4xwh


==Crystal structure of the human N-acetyl-alpha-glucosaminidase==
<StructureSection load='4xwh' size='340' side='right'caption='[[4xwh]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xwh]] is a 1 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=4XWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XWH 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]] 2.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NEP:N1-PHOSPHONOHISTIDINE'>NEP</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</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=4xwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xwh OCA], [https://pdbe.org/4xwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xwh RCSB], [https://www.ebi.ac.uk/pdbsum/4xwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xwh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ANAG_HUMAN ANAG_HUMAN] Sanfilippo syndrome type B. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ANAG_HUMAN ANAG_HUMAN] Involved in the degradation of heparan sulfate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mucopolysaccharidosis III B (MPS III-B) is a rare lysosomal storage disorder caused by deficiencies in Alpha-N-acetylglucosaminidase (NAGLU) for which there is currently no cure, and present treatment is largely supportive. Understanding the structure of NAGLU may allow for identification of novel therapeutic targets for MPS III-B. Here we describe the first crystal structure of human NAGLU, determined to a resolution of 2.3A. The crystal structure reveals a novel homotrimeric configuration, maintained primarily by hydrophobic and electrostatic interactions via domain II of three contiguous domains from the N- to C-terminus. The active site cleft is located between domains II and III. Catalytic glutamate residues, E316 and E446, are located at the top of the (alpha/beta)8 barrel structure in domain II. We utilized the three-dimensional structure of NAGLU to map several MPS III-B mutations, and hypothesize their functional consequences. Revealing atomic level structural information about this critical lysosomal enzyme paves the way for the design of novel therapeutics to target the underlying causes of MPS III-B.

Structural characterization of the alpha-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B.,Birrane G, Dassier AL, Romashko A, Lundberg D, Holmes K, Cottle T, Norton AW, Zhang B, Concino MF, Meiyappan M J Struct Biol. 2019 Mar 1;205(3):65-71. doi: 10.1016/j.jsb.2019.02.005. Epub 2019, Feb 23. PMID:30802506<ref>PMID:30802506</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xwh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Birrane G]]
[[Category: Dassier A]]
[[Category: Meiyappan M]]