View source for 2vur


==Chemical dissection of the link between Streptozotocin, O-GlcNAc and pancreatic cell death==
<StructureSection load='2vur' size='340' side='right'caption='[[2vur]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vur]] 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=2VUR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VUR 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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YX1:2-DEOXY-2-{[(2-HYDROXY-1-METHYLHYDRAZINO)CARBONYL]AMINO}-BETA-D-GLUCOPYRANOSE'>YX1</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=2vur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vur OCA], [https://pdbe.org/2vur PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vur RCSB], [https://www.ebi.ac.uk/pdbsum/2vur PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vur 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/vu/2vur_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=2vur ConSurf].
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== Publication Abstract from PubMed ==
Streptozotocin is a natural product that selectively kills insulin-secreting beta cells, and is widely used to generate mouse models of diabetes or treat pancreatic tumors. Several studies suggest that streptozotocin toxicity stems from its N-nitrosourea moiety releasing nitric oxide and possessing DNA alkylating activity. However, it has also been proposed that streptozotocin induces apoptosis by inhibiting O-GlcNAcase, an enzyme that, together with O-GlcNAc transferase, is important for dynamic intracellular protein O-glycosylation. We have used galacto-streptozotocin to chemically dissect the link between O-GlcNAcase inhibition and apoptosis. Using X-ray crystallography, enzymology, and cell biological studies on an insulinoma cell line, we show that, whereas streptozotocin competitively inhibits O-GlcNAcase and induces apoptosis, its galacto-configured derivative no longer inhibits O-GlcNAcase, yet still induces apoptosis. This supports a general chemical poison mode of action for streptozotocin, suggesting the need for using more specific inhibitors to study protein O-GlcNAcylation.

Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic cell death.,Pathak S, Dorfmueller HC, Borodkin VS, van Aalten DM Chem Biol. 2008 Aug 25;15(8):799-807. PMID:18721751<ref>PMID:18721751</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 2vur" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]]
*[[O-GlcNAcase|O-GlcNAcase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Large Structures]]
[[Category: Borodkin VS]]
[[Category: Dorfmueller HC]]
[[Category: Pathak S]]
[[Category: Van Aalten DMF]]