2cbi: Difference between revisions

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-[[Image:2cbi.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2cbi", creates the "Structure Box" on the page.
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-{{STRUCTURE_2cbi|  PDB=2cbi  |  SCENE=  }}
-'''STRUCTURE OF THE CLOSTRIDIUM PERFRINGENS NAGJ FAMILY 84 GLYCOSIDE HYDROLASE, A HOMOLOGUE OF HUMAN O-GLCNACASE'''
+==Structure of the Clostridium perfringens NagJ family 84 glycoside hydrolase, a homologue of human O-GlcNAcase==
+<StructureSection load='2cbi' size='340' side='right'caption='[[2cbi]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2cbi]] 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=2CBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBI 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]] 2.25&#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=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2cbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbi OCA], [https://pdbe.org/2cbi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cbi RCSB], [https://www.ebi.ac.uk/pdbsum/2cbi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbi 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/cb/2cbi_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=2cbi ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+O-linked N-acetylglucosamine (O-GlcNAc) modification of specific serines/threonines on intracellular proteins in higher eukaryotes has been shown to directly regulate important processes such as the cell cycle, insulin sensitivity and transcription. The structure, molecular mechanisms of catalysis, protein substrate recognition/specificity of the eukaryotic O-GlcNAc transferase and hydrolase are largely unknown. Here we describe the crystal structure, enzymology and in vitro activity on human substrates of Clostridium perfringens NagJ, a close homologue of human O-GlcNAcase (OGA), representing the first family 84 glycoside hydrolase structure. The structure reveals a deep active site pocket highly conserved with the human enzyme, compatible with binding of O-GlcNAcylated peptides. Together with mutagenesis data, the structure supports a variant of the substrate-assisted catalytic mechanism, involving two aspartic acids and an unusually positioned tyrosine. Insights into recognition of substrate come from a complex with the transition state mimic O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (Ki=5.4 nM). Strikingly, the enzyme is inhibited by the pseudosubstrate peptide Ala-Cys(-S-GlcNAc)-Ala, and has OGA activity against O-GlcNAcylated human proteins, suggesting that the enzyme is a suitable model for further studies into the function of human OGA.
-==Overview==
+Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis.,Rao FV, Dorfmueller HC, Villa F, Allwood M, Eggleston IM, van Aalten DM EMBO J. 2006 Apr 5;25(7):1569-78. Epub 2006 Mar 16. PMID:16541109<ref>PMID:16541109</ref>
-O-linked N-acetylglucosamine (O-GlcNAc) modification of specific serines/threonines on intracellular proteins in higher eukaryotes has been shown to directly regulate important processes such as the cell cycle, insulin sensitivity and transcription. The structure, molecular mechanisms of catalysis, protein substrate recognition/specificity of the eukaryotic O-GlcNAc transferase and hydrolase are largely unknown. Here we describe the crystal structure, enzymology and in vitro activity on human substrates of Clostridium perfringens NagJ, a close homologue of human O-GlcNAcase (OGA), representing the first family 84 glycoside hydrolase structure. The structure reveals a deep active site pocket highly conserved with the human enzyme, compatible with binding of O-GlcNAcylated peptides. Together with mutagenesis data, the structure supports a variant of the substrate-assisted catalytic mechanism, involving two aspartic acids and an unusually positioned tyrosine. Insights into recognition of substrate come from a complex with the transition state mimic O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (Ki=5.4 nM). Strikingly, the enzyme is inhibited by the pseudosubstrate peptide Ala-Cys(-S-GlcNAc)-Ala, and has OGA activity against O-GlcNAcylated human proteins, suggesting that the enzyme is a suitable model for further studies into the function of human OGA.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-CBI is a [[Single protein]] structure of sequence 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=2CBI OCA].
+</div>
+<div class="pdbe-citations 2cbi" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis., Rao FV, Dorfmueller HC, Villa F, Allwood M, Eggleston IM, van Aalten DM, EMBO J. 2006 Apr 5;25(7):1569-78. Epub 2006 Mar 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16541109 16541109]
+*[[Hyaluronidase 3D structures|Hyaluronidase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Clostridium perfringens]]
-[[Category: Hyalurononglucosaminidase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Allwood M]]
-[[Category: Aalten, D M.F Van.]]
+[[Category: Dorfmueller HC]]
-[[Category: Allwood, M.]]
+[[Category: Eggleston IM]]
-[[Category: Dorfmueller, H C.]]
+[[Category: Rao FV]]
-[[Category: Eggleston, I M.]]
+[[Category: Villa F]]
-[[Category: Rao, F V.]]
+[[Category: Van Aalten DMF]]
-[[Category: Villa, F.]]
-[[Category: Carbohydrate]]
-[[Category: Family 84 glycoside hydrolase]]
-[[Category: Glycoside hydrolase]]
-[[Category: Hyaluronidase]]
-[[Category: Hydrolase]]
-[[Category: O-glcnac]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:39:18 2008''