4WYY

Crystal Structure of P. aeruginosa AmpC

Summary for 4WYY

• Entry DOI: 10.2210/pdb4wyy/pdb
• Related: 4WZ4 4WZ5
• Descriptor: Beta-lactamase, GLYCEROL, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: beta lactamase, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
• Cellular location: Periplasm : P24735
• Total number of polymer chains: 1
• Total formula weight: 40260.15

Authors

Ferguson, A.D. (deposition date: 2014-11-18, release date: 2015-08-05, Last modification date: 2024-11-20)

Primary citation

McKinney, D.C.,Zhou, F.,Eyermann, C.J.,Ferguson, A.D.,Prince, D.B.,Breen, J.,Giacobbe, R.A.,Lahiri, S.,Verheijen, J.C.
4,5-Disubstituted 6-Aryloxy-1,3-dihydrobenzo[c][1,2]oxaboroles Are Broad-Spectrum Serine beta-Lactamase Inhibitors.
ACS Infect Dis, 1:310-316, 2015

PubMed Abstract: Bacterially expressed β-lactamases are rapidly eroding the clinical utility of the important β-lactam class of antibacterials, significantly impairing our ability to fight serious bacterial infections. This paper describes a study of oxaborole-derived β-lactamase inhibitors in which crystal structures and computational modeling aided in the rational design of analogues with improved spectrum of activity against class A, C, and D enzymes. Crystal structures of two of these inhibitors covalently bound to two different serine β-lactamases, class C Pseudomonas aeruginosa AmpC and class D OXA-10, are described herein. Improved physicochemical properties as well as increased activity against an array of β-lactamases resulted in substantial restoration of susceptibility to ceftazidime in Escherichia coli and Klebsiella pneumoniae.

PubMed: 27622821
DOI: 10.1021/acsinfecdis.5b00031

Experimental method

X-RAY DIFFRACTION (1.28 Å)