5fap | pdb_00005fap

CTX-M-15 in complex with FPI-1602

spinqualitylabelsall models 5fap, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fap is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 602 Related: 5fao, 5fa7, 5faq, 5fas, 5fat Gene: blaUOE-1, bla, bla CTX-M-15, bla_1, bla_2, bla_3, blaCTX-M-15, blaCTX-M15, CTX-M-15, ECONIH1_02760, ECONIH1_27135, ERS085368_04262, ERS085370_01802, ERS085377_05268, ERS139214_01914, ERS139238_04648, ERS139238_04652, ERS150880_04508, HUS2011_pI0012, pCTXM15_EC8_00003, SK84_05077, SK86_03319 ("Bacillus coli" Migula 1895) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Avibactam is a diazabicyclooctane beta-lactamase inhibitor possessing outstanding but incomplete efficacy against multidrug-resistant Gram-negative pathogens in combination with beta-lactam antibiotics. Significant pharmaceutical investment in generating derivatives of avibactam warrants a thorough characterization of their activity. We show here through structural and kinetic analysis that select diazabicyclooctane derivatives display effective but varied inhibition of two clinically important beta-lactamases (CTX-M-15 and OXA-48). Furthermore, these derivatives exhibit considerable antimicrobial activity (MIC </= 2 mug/mL) against clinical isolates of Pseudomonas aeruginosa, Escherichia coli, and Enterobacter spp. Imaging of cell phenotype along with structural and biochemical experiments unambiguously demonstrate that this activity, in E. coli, is a result of targeting penicillin-binding protein 2. Our results suggest that structure-activity relationship studies for the purpose of drug discovery must consider both beta-lactamases and penicillin-binding proteins as targets. We believe that this approach will yield next-generation combination or monotherapies with an expanded spectrum of activity against currently untreatable Gram-negative pathogens. Structural and Kinetic Characterization of Diazabicyclooctanes as Dual Inhibitors of Both Serine-beta-Lactamases and Penicillin-Binding Proteins.,King AM, King DT, French S, Brouillette E, Asli A, Alexander JA, Vuckovic M, Maiti SN, Parr TR Jr, Brown ED, Malouin F, Strynadka NC, Wright GD ACS Chem Biol. 2016 Jan 14. PMID:26731698 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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