4xuz | pdb_00004xuz

Structure of CTX-M-15 bound to RPX-7009 at 1.5 A

spinqualitylabelsall models 4xuz, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xuz is a 1 chain structure with sequence from Klebsiella pneumoniae subsp. pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4D6, CIT, CL, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S5LVN3_KLEPN Publication Abstract from PubMed The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria. Discovery of a Cyclic Boronic Acid beta-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases.,Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN J Med Chem. 2015 Mar 17. PMID:25782055 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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