View source for 5ne1


==L2 class A serine-beta-lactamase in complex with cyclic boronate 2==
<StructureSection load='5ne1' size='340' side='right'caption='[[5ne1]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ne1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NE1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OK3:(R)-3-(4-(AMINOMETHYL)BENZAMIDO)-8-CARBOXY-2,2-DIHYDROXY-3,4-DIHYDRO-2H-BENZO[E][1,2]OXABORININ-2-UIDE'>OK3</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5ne1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ne1 OCA], [https://pdbe.org/5ne1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ne1 RCSB], [https://www.ebi.ac.uk/pdbsum/5ne1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ne1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9RBQ1_STEMA Q9RBQ1_STEMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Clavulanic 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<ref>PMID:28876489</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ne1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Stenotrophomonas maltophilia]]
[[Category: Calvopina K]]
[[Category: Hinchliffe P]]
[[Category: Spencer J]]