2xm2: Difference between revisions
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<StructureSection load='2xm2' size='340' side='right'caption='[[2xm2]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='2xm2' size='340' side='right'caption='[[2xm2]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xm2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2xm2]] is a 2 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=2XM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XM2 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LOG:LOGNAC'>LOG</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=2xm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xm2 OCA], [https://pdbe.org/2xm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xm2 RCSB], [https://www.ebi.ac.uk/pdbsum/2xm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xm2 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=2xm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xm2 OCA], [https://pdbe.org/2xm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xm2 RCSB], [https://www.ebi.ac.uk/pdbsum/2xm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xm2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Bacteroides thetaiotaomicron VPI-5482]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Davies | [[Category: Davies GJ]] | ||
[[Category: He | [[Category: He Y]] | ||
Latest revision as of 13:34, 20 December 2023
BtGH84 in complex with LOGNAcBtGH84 in complex with LOGNAc
Structural highlights
FunctionOGA_BACTN Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMedThe dynamic, intracellular, O-GlcNAc modification is of continuing interest and one whose study through targeted "chemical genetics" approaches is set to increase. Of particular importance is the inhibition of the O-GlcNAc hydrolase, O-GlcNAcase (OGA), since this provides a route to elevate cellular O-GlcNAc levels, and subsequent phenotypic evaluation. Such a small molecule approach complements other methods and potentially avoids changes in protein-protein interactions that manifest themselves in molecular biological approaches to O-GlcNAc transferase knockout or over-expression. Here we describe the kinetic, thermodynamic and three-dimensional structural analysis of a bacterial OGA analogue from Bacteroides thetaiotaomicron, BtGH84, in complex with a lactone oxime (LOGNAc) and a lactam form of N-acetylglucosamine and compare their binding signatures with that of the more potent inhibitor O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc). We show that both LOGNAc and the N-acetyl gluconolactam are significantly poorer inhibitors than PUGNAc, which may reflect poorer mimicry of transition state geometry and steric clashes with the enzyme upon binding; drawbacks that the phenyl carbamate adornment of PUGNAc helps mitigate. Implications for the design of future generations of inhibitors are discussed. Inhibition of a bacterial O-GlcNAcase homologue by lactone and lactam derivatives: structural, kinetic and thermodynamic analyses.,He Y, Bubb AK, Stubbs KA, Gloster TM, Davies GJ Amino Acids. 2011 Mar;40(3):829-39. Epub 2010 Aug 6. PMID:20689974[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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