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| | <StructureSection load='2cbj' size='340' side='right'caption='[[2cbj]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='2cbj' size='340' side='right'caption='[[2cbj]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cbj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898]. The September 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''O-GlcNAc Transferase'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_9 10.2210/rcsb_pdb/mom_2011_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cbj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. The September 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''O-GlcNAc Transferase'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_9 10.2210/rcsb_pdb/mom_2011_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CBJ FirstGlance]. <br> |
| - | </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=OAN:O-(2-ACETAMIDO-2-DEOXY+D-GLUCOPYRANOSYLIDENE)+AMINO-N-PHENYLCARBAMATE'>OAN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cbi|2cbi]]</div></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=OAN:O-(2-ACETAMIDO-2-DEOXY+D-GLUCOPYRANOSYLIDENE)+AMINO-N-PHENYLCARBAMATE'>OAN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2cbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbj OCA], [https://pdbe.org/2cbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cbj RCSB], [https://www.ebi.ac.uk/pdbsum/2cbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbj ProSAT]</span></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=2cbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cbj OCA], [https://pdbe.org/2cbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cbj RCSB], [https://www.ebi.ac.uk/pdbsum/2cbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cbj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/OGA_CLOPE 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]
| + | [https://www.uniprot.org/uniprot/OGA_CLOP1 OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus perfringens veillon and zuber 1898]] | + | [[Category: Clostridium perfringens]] |
| - | [[Category: Hydrolase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: O-GlcNAc Transferase]] | | [[Category: O-GlcNAc Transferase]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Aalten, D M.F van]]
| + | [[Category: Allwood M]] |
| - | [[Category: Allwood, M]] | + | [[Category: Dorfmueller HC]] |
| - | [[Category: Dorfmueller, H C]] | + | [[Category: Eggleston IM]] |
| - | [[Category: Eggleston, I M]] | + | [[Category: Rao FV]] |
| - | [[Category: Rao, F V]] | + | [[Category: Villa F]] |
| - | [[Category: Villa, F]] | + | [[Category: Van Aalten DMF]] |
| - | [[Category: Carbohydrate]] | + | |
| - | [[Category: Family 84 glycoside hydrolase]]
| + | |
| - | [[Category: Glycoside hydrolase]]
| + | |
| - | [[Category: Hyaluronidase]]
| + | |
| - | [[Category: O-glcnac]]
| + | |
| Structural highlights
Function
OGA_CLOP1 Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.
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 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.
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.
See Also
References
- ↑ Rao FV, Dorfmueller HC, Villa F, Allwood M, Eggleston IM, van Aalten DM. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. EMBO J. 2006 Apr 5;25(7):1569-78. Epub 2006 Mar 16. PMID:16541109
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