6i30

Crystal structure of the AmpC from Pseudomonas aeruginosa with 1C

spinqualitylabelsall models 6i30, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6i30 is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: C6S Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2Z4BUZ1_PSEAI Publication Abstract from PubMed BACKGROUND: The beta-lactam antibiotics represent the most successful drug class for treatment of bacterial infections. Resistance to them, importantly via production of beta-lactamases, which collectively are able to hydrolyse all classes of beta-lactams, threatens their continued widespread use. Bicyclic boronates show potential as broad spectrum inhibitors of the mechanistically distinct serine- (SBL) and metallo- (MBL) beta-lactamase families. METHODS: Using biophysical methods, including crystallographic analysis, we have investigated the binding mode of bicyclic boronates to clinically important beta-lactamases. Induction experiments and agar-based MIC screening against MDR-Enterobacteriaceae (n=132) were used to evaluate induction properties and the in vitro efficacy of a bicyclic boronate in combination with meropenem. RESULTS: Crystallographic analysis of a bicyclic boronate in complex with AmpC from Pseudomonas aeruginosa reveals it binds to form a tetrahedral boronate species. Microbiological studies on the clinical coverage (in combination with meropenem) and induction of beta-lactamases by bicyclic boronates further support the promise of such compounds as broad spectrum beta-lactamase inhibitors. CONCLUSIONS: Together with reported studies on the structural basis of their inhibition of class A, B and D beta-lactamases, biophysical studies, including crystallographic analysis, support the proposal that bicyclic boronates mimic tetrahedral intermediates common to SBL and MBL catalysis. GENERAL SIGNIFICANCE: Bicyclic boronates are a new generation of broad spectrum inhibitors of both SBLs and MBLs. Studies on the inhibition of AmpC and other beta-lactamases by cyclic boronates.,Cahill ST, Tyrrell JM, Navratilova IH, Calvopina K, Robinson SW, Lohans CT, McDonough MA, Cain R, Fishwick CWG, Avison MB, Walsh TR, Schofield CJ, Brem J Biochim Biophys Acta Gen Subj. 2019 Apr;1863(4):742-748. doi:, 10.1016/j.bbagen.2019.02.004. Epub 2019 Feb 7. PMID:30738906 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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