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| | ==BtGH84 structure in complex with PUGNAc== | | ==BtGH84 structure in complex with PUGNAc== |
| - | <StructureSection load='2vvs' size='340' side='right' caption='[[2vvs]], [[Resolution|resolution]] 2.24Å' scene=''> | + | <StructureSection load='2vvs' size='340' side='right'caption='[[2vvs]], [[Resolution|resolution]] 2.24Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vvs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VVS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vvs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VVS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.24Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vvn|2vvn]], [[2jiw|2jiw]], [[2chn|2chn]], [[2j4g|2j4g]], [[2j47|2j47]], [[2cho|2cho]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </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=2vvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vvs OCA], [https://pdbe.org/2vvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vvs RCSB], [https://www.ebi.ac.uk/pdbsum/2vvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vvs ProSAT]</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=2vvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vvs OCA], [http://pdbe.org/2vvs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vvs RCSB], [http://www.ebi.ac.uk/pdbsum/2vvs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vvs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN]] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. | + | [https://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN] 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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| | ==See Also== | | ==See Also== |
| | *[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | | *[[Beta-Hexosaminidase|Beta-Hexosaminidase]] |
| | + | *[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]] |
| | + | *[[O-GlcNAcase|O-GlcNAcase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bactn]] | + | [[Category: Bacteroides thetaiotaomicron VPI-5482]] |
| - | [[Category: Beta-N-acetylhexosaminidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bubb, A]] | + | [[Category: Bubb A]] |
| - | [[Category: Davies, G J]] | + | [[Category: Davies GJ]] |
| - | [[Category: Macauley, M S]] | + | [[Category: Macauley MS]] |
| - | [[Category: Martinez-Fleites, C]] | + | [[Category: Martinez-Fleites C]] |
| - | [[Category: Vocadlo, D J]] | + | [[Category: Vocadlo DJ]] |
| - | [[Category: Glycoside hydrolase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: O-glcnac]]
| + | |
| Structural highlights
Function
OGA_BACTN 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
The O-GlcNAc post-translational modification is considered to act as a sensor of nutrient flux through the hexosamine biosynthetic pathway. A cornerstone of this hypothesis is that global elevation of protein O-GlcNAc levels, typically induced with the non-selective O-GlcNAcase inhibitor PUGNAc (O-(2-acetamido-2-deoxy-D-glycopyranosylidene) amino-N-phenylcarbamate), causes insulin resistance in adipocytes. Here we address the potential link between elevated O-GlcNAc and insulin resistance by using a potent and selective inhibitor of O-GlcNAcase (NButGT (1,2-dideoxy-2'-propyl-alpha-D-glucopyranoso-[2,1-D]-Delta 2'-thiazoline), 1200-fold selectivity). A comparison of the structures of a bacterial homologue of O-GlcNAcase in complex with PUGNAc or NButGT reveals that these inhibitors bind to the same region of the active site, underscoring the competitive nature of their inhibition of O-GlcNAcase and the molecular basis of selectivity. Treating 3T3-L1 adipocytes with NButGT induces rapid increases in global O-GlcNAc levels, but strikingly, NButGT treatment does not replicate the insulin desensitizing effects of the non-selective O-GlcNAcase inhibitor PUGNAc. Consistent with these observations, NButGT also does not recapitulate the impaired insulin-mediated phosphorylation of Akt that is induced by treatment with PUGNAc. Collectively, these results suggest that increases in global levels of O-GlcNAc-modified proteins of cultured adipocytes do not, on their own, cause insulin resistance.
Elevation of global O-GlcNAc levels in 3T3-L1 adipocytes by selective inhibition of O-GlcNAcase does not induce insulin resistance.,Macauley MS, Bubb AK, Martinez-Fleites C, Davies GJ, Vocadlo DJ J Biol Chem. 2008 Dec 12;283(50):34687-95. Epub 2008 Oct 8. PMID:18842583[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Macauley MS, Bubb AK, Martinez-Fleites C, Davies GJ, Vocadlo DJ. Elevation of global O-GlcNAc levels in 3T3-L1 adipocytes by selective inhibition of O-GlcNAcase does not induce insulin resistance. J Biol Chem. 2008 Dec 12;283(50):34687-95. Epub 2008 Oct 8. PMID:18842583 doi:10.1074/jbc.M804525200
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