2xm2: Difference between revisions

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-[[Image:2xm2.png|left|200px]]
+==BTGH84 IN COMPLEX WITH LOGNAC==
+<StructureSection load='2xm2' size='340' side='right' caption='[[2xm2]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2xm2]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XM2 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LOG:LOGNAC'>LOG</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vvn|2vvn]], [[2wzh|2wzh]], [[2w67|2w67]], [[2wca|2wca]], [[2vvs|2vvs]], [[2j4g|2j4g]], [[2w4x|2w4x]], [[2xm1|2xm1]], [[2cho|2cho]], [[2xj7|2xj7]], [[2jiw|2jiw]], [[2chn|2chn]], [[2x0h|2x0h]], [[2wzi|2wzi]], [[2j47|2j47]], [[2w66|2w66]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xm2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xm2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xm2 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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.
-{{STRUCTURE_2xm2|  PDB=2xm2  |  SCENE=  }}
+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<ref>PMID:20689974</ref>
-===BTGH84 IN COMPLEX WITH LOGNAC===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_20689974}}
-==About this Structure==
-[[2xm2]] is a 2 chain structure with sequence from [http://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].
 ==See Also==
 *[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020689974</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Bacteroides thetaiotaomicron vpi-5482]]
 [[Category: Beta-N-acetylhexosaminidase]]