4WZ5

Crystal structure of P. aeruginosa OXA10

Summary for 4WZ5

• Entry DOI: 10.2210/pdb4wz5/pdb
• Related: 4WYY 4WZ4
• Descriptor: Beta-lactamase OXA-10, SULFATE ION, {(3R)-6-[(3-amino-1,2,4-thiadiazol-5-yl)oxy]-1-hydroxy-4,5-dimethyl-1,3-dihydro-2,1-benzoxaborol-3-yl}acetic acid, ... (6 entities in total)
• Functional Keywords: beta lactamase, inhibtor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Pseudomonas aeruginosa; More
• Total number of polymer chains: 4
• Total formula weight: 112943.29

Authors

Ferguson, A.D. (deposition date: 2014-11-18, release date: 2015-08-05, Last modification date: 2016-09-28)

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 (1.6 Å)