View source for 2j62


==Structure of a bacterial O-glcnacase in complex with glcnacstatin==
<StructureSection load='2j62' size='340' side='right'caption='[[2j62]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2j62]] is a 2 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=2J62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J62 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]] 2.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GSZ:N-[(5R,6R,7R,8S)-6,7-DIHYDROXY-5-(HYDROXYMETHYL)-2-(2-PHENYLETHYL)-1,5,6,7,8,8A-HEXAHYDROIMIDAZO[1,2-A]PYRIDIN-8-YL]-2-METHYLPROPANAMIDE'>GSZ</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=2j62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j62 OCA], [https://pdbe.org/2j62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j62 RCSB], [https://www.ebi.ac.uk/pdbsum/2j62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j62 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OGA_CLOP1 OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.
== 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/j6/2j62_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=2j62 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many phosphorylation signal transduction pathways in the eukaryotic cell are modulated by posttranslational modification of specific serines/threonines with N-acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate biological processes as diverse as the cell cycle, insulin signaling, and protein degradation. The two enzymes involved in this dynamic and abundant modification are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently revealed that the O-GlcNAcase possesses an active site with significant structural similarity to that of the human lysosomal hexosaminidases HexA/HexB. PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human cell lines, also inhibits these hexosaminidases. Here, we have exploited recent structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition state as revealed by X-ray crystallography. This compound is able to raise O-GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus provides a novel, potent tool for the study of the role of O-GlcNAc in intracellular signal transduction pathways.

GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels.,Dorfmueller HC, Borodkin VS, Schimpl M, Shepherd SM, Shpiro NA, van Aalten DM J Am Chem Soc. 2006 Dec 27;128(51):16484-5. PMID:17177381<ref>PMID:17177381</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 2j62" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hyaluronidase 3D structures|Hyaluronidase 3D structures]]
*[[O-GlcNAcase|O-GlcNAcase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Large Structures]]
[[Category: Borodkin VS]]
[[Category: Dorfmueller HC]]
[[Category: Schimpl M]]
[[Category: Shepherd SM]]
[[Category: Shpiro NA]]
[[Category: Van Aalten DMF]]