5ne2 | pdb_00005ne2

L2 class A serine-beta-lactamase

spinqualitylabelsall models 5ne2, resolution 1.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ne2 is a 2 chain structure with sequence from Stenotrophomonas maltophilia. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.19Å Ligands: DGL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9RBQ1_STEMA 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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