2cbi: Difference between revisions
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==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]] 2.25Å' scene=''> | <StructureSection load='2cbi' size='340' side='right' caption='[[2cbi]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cbj|2cbj]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cbj|2cbj]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.35 3.2.1.35] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.35 3.2.1.35] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbi OCA], [http://pdbe.org/2cbi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cbi RCSB], [http://www.ebi.ac.uk/pdbsum/2cbi PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbi OCA], [http://pdbe.org/2cbi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cbi RCSB], [http://www.ebi.ac.uk/pdbsum/2cbi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cb/2cbi_consurf.spt"</scriptWhenChecked> | <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> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2cbi" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2cbi" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Bacillus perfringens veillon and zuber 1898]] | [[Category: Bacillus perfringens veillon and zuber 1898]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Aalten, D M.F | [[Category: Aalten, D M.F van]] | ||
[[Category: Allwood, M]] | [[Category: Allwood, M]] | ||
[[Category: Dorfmueller, H C]] | [[Category: Dorfmueller, H C]] | ||
Revision as of 09:54, 28 February 2018
Structure of the Clostridium perfringens NagJ family 84 glycoside hydrolase, a homologue of human O-GlcNAcaseStructure of the Clostridium perfringens NagJ family 84 glycoside hydrolase, a homologue of human O-GlcNAcase
Structural highlights
Function[OGA_CLOPE] Binds carbohydrates. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Can bind and deglycosylate O-glycosylated peptides from mammals. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates (in vitro).[UniProtKB:Q0TR53] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedO-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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