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PDBsum entry 4wz4
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Hydrolase/hydrolase inhibitor
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PDB id
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4wz4
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References listed in PDB file
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Key reference
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Title
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4,5-Disubstituted 6-Aryloxy-1,3-Dihydrobenzo[c][1,2]oxaboroles are broad-Spectrum serine β-Lactamase inhibitors.
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Authors
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D.C.Mckinney,
F.Zhou,
C.J.Eyermann,
A.D.Ferguson,
D.B.Prince,
J.Breen,
R.A.Giacobbe,
S.Lahiri,
J.C.Verheijen.
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Ref.
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Acs Infect Dis, 2015,
1,
310-316.
[DOI no: ]
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PubMed id
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Abstract
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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.
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