View source for 2vcb


==Family 89 Glycoside Hydrolase from Clostridium perfringens in complex with PUGNAc==
<StructureSection load='2vcb' size='340' side='right'caption='[[2vcb]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vcb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VCB 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]] 2.2&#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=OAN:O-(2-ACETAMIDO-2-DEOXY+D-GLUCOPYRANOSYLIDENE)+AMINO-N-PHENYLCARBAMATE'>OAN</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=2vcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vcb OCA], [https://pdbe.org/2vcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vcb RCSB], [https://www.ebi.ac.uk/pdbsum/2vcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vcb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2YU91_CLOP1 A0A0H2YU91_CLOP1] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vc/2vcb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vcb ConSurf].
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== Publication Abstract from PubMed ==
Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for &gt;20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB.,Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, Boraston AB Proc Natl Acad Sci U S A. 2008 May 6;105(18):6560-5. Epub 2008 Apr 28. PMID:18443291<ref>PMID:18443291</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2vcb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Large Structures]]
[[Category: Berg O]]
[[Category: Boraston AB]]
[[Category: Ficko-Blean E]]
[[Category: Stubbs KA]]
[[Category: Vocadlo DJ]]