5ne2: Difference between revisions
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==L2 class A serine-beta-lactamase== | ==L2 class A serine-beta-lactamase== | ||
<StructureSection load='5ne2' size='340' side='right' caption='[[5ne2]], [[Resolution|resolution]] 1.19Å' scene=''> | <StructureSection load='5ne2' size='340' side='right'caption='[[5ne2]], [[Resolution|resolution]] 1.19Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ne2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NE2 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5ne2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NE2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NE2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</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-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ne2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ne2 OCA], [http://pdbe.org/5ne2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ne2 RCSB], [http://www.ebi.ac.uk/pdbsum/5ne2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ne2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ne2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ne2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Large Structures]] | |||
[[Category: Calvopina, K]] | [[Category: Calvopina, K]] | ||
[[Category: Hinchliffe, P]] | [[Category: Hinchliffe, P]] | ||
Revision as of 15:03, 26 August 2020
L2 class A serine-beta-lactamaseL2 class A serine-beta-lactamase
Structural highlights
Publication Abstract from PubMedClavulanic acid and avibactam are clinically deployed serine beta-lactamase inhibitors, important as a defence against antibacterial resistance. Bicyclic boronates are recently discovered inhibitors of serine and some metallo beta-lactamases. Here we show that avibactam and a bicyclic boronate inhibit L2 (serine beta-lactamase) but not L1 (metallo beta-lactamase) from the extensively drug resistant human pathogen Stenotrophomonas maltophilia. X-ray crystallography revealed that both inhibitors bind L2 by covalent attachment to the nucleophilic serine. Both inhibitors reverse ceftazidime resistance in S. maltophilia because, unlike clavulanic acid, they do not induce L1 production. Ceftazidime/inhibitor resistant mutants hyper-produce L1, but retain aztreonam/inhibitor susceptibility because aztreonam is not an L1 substrate. Importantly, avibactam, but not the bicyclic boronate is deactivated by L1 at a low rate; the utility of avibactam might be compromised by mutations that increase this deactivation rate. These data rationalize the observed clinical efficacy of ceftazidime/avibactam plus aztreonam as combination therapy for S. maltophilia infections and confirm that aztreonam-like beta-lactams plus non-classical beta-lactamase inhibitors, particularly avibactam-like and bicyclic boronate compounds, have potential for treating infections caused by this most intractable of drug resistant pathogens. This article is protected by copyright. All rights reserved. Structural/mechanistic insights into the efficacy of non-classical beta-lactamase inhibitors against extensively drug resistant Stenotrophomonas maltophilia clinical isolates.,Calvopina K, Hinchliffe P, Brem J, Heesom KJ, Johnson S, Cain R, Lohans CT, Fishwick CWG, Schofield CJ, Spencer J, Avison MB Mol Microbiol. 2017 Sep 6. doi: 10.1111/mmi.13831. PMID:28876489[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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