2wb5: Difference between revisions

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-{{Seed}}
-[[Image:2wb5.jpg|left|200px]]
-<!--
+==GlcNAcstatins are nanomolar inhibitors of human O-GlcNAcase inducing cellular hyper-O-GlcNAcylation==
-The line below this paragraph, containing "STRUCTURE_2wb5", creates the "Structure Box" on the page.
+<StructureSection load='2wb5' size='340' side='right'caption='[[2wb5]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wb5]] 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=2WB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WB5 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VGB:(5R,6R,7R,8S)-6,7-DIHYDROXY-5-(HYDROXYMETHYL)-2-(2-PHENYLETHYL)-8-(PROPANOYLAMINO)-5,6,7,8-TETRAHYDRO-1H-IMIDAZO[1,2-A]PYRIDIN-4-IUM'>VGB</scene></td></tr>
-{{STRUCTURE_2wb5|  PDB=2wb5  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wb5 OCA], [https://pdbe.org/2wb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wb5 RCSB], [https://www.ebi.ac.uk/pdbsum/2wb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wb5 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/wb/2wb5_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=2wb5 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+O-GlcNAcylation is an essential, dynamic and inducible posttranslational glycosylation of cytosolic proteins in metazoa and can show interplay with protein phosphorylation. Inhibition of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from O-GlcNAcylated proteins, is a useful strategy to probe the role of this modification in a range of cellular processes. Here, we report the rational design and evaluation of GlcNAcstatins, a family of potent, competitive and selective inhibitors of human OGA. Kinetic experiments with recombinant human OGA reveal that the GlcNAcstatins are the most potent human OGA inhibitors reported to date, inhibiting the enzyme in the sub-nanomolar to nanomolar range. Modification of the GlcNAcstatin N-acetyl group leads to up to 160-fold selectivity against the human lysosomal hexosaminidases which employ a similar substrate-assisted catalytic mechanism. Mutagenesis studies in a bacterial OGA, guided by the structure of a GlcNAcstatin complex, provides insight into the role of conserved residues in the human OGA active site. GlcNAcstatins are cell-permeable and, at low nanomolar concentrations, effectively modulate intracellular O-GlcNAc levels through inhibition of OGA, in a range of human cell lines. Thus, these compounds are potent, selective tools to study the cell biology of O-GlcNAc.
-===GLCNACSTATINS ARE NANOMOLAR INHIBITORS OF HUMAN O-GLCNACASE INDUCING CELLULAR HYPER-O-GLCNACYLATION===
+GlcNAcstatins are nanomolar inhibitors of human O-GlcNAcase inducing cellular hyper-O-GlcNAcylation.,Dorfmueller HC, Borodkin VS, Schimpl M, van Aalten DM Biochem J. 2009 Mar 10. PMID:19275764<ref>PMID:19275764</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2wb5" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19275764}}, adds the Publication Abstract to the page
+*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19275764 is the PubMed ID number.
+*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]]
--->
+*[[O-GlcNAcase|O-GlcNAcase]]
-{{ABSTRACT_PUBMED_19275764}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-WB5 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WB5 OCA].
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:19275764</ref><references group="xtra"/>
 [[Category: Clostridium perfringens]]
-[[Category: Aalten, D M.F Van.]]
+[[Category: Large Structures]]
-[[Category: Borodkin, V S.]]
+[[Category: Borodkin VS]]
-[[Category: Dorfmueller, H C.]]
+[[Category: Dorfmueller HC]]
-[[Category: Schimpl, M.]]
+[[Category: Schimpl M]]
-[[Category: Coiled coil]]
+[[Category: Van Aalten DMF]]
-[[Category: Glycosidase]]
-[[Category: Hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr  2 15:22:53 2009''