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PDBsum entry 5dts
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References listed in PDB file
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Key reference
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Title
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Screening and design of inhibitor scaffolds for the antibiotic resistance oxacillinase-48 (oxa-48) through surface plasmon resonance screening.
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Authors
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B.A.Lund,
T.Christopeit,
Y.Guttormsen,
A.Bayer,
H.K.Leiros.
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Ref.
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J Med Chem, 2016,
59,
5542-5554.
[DOI no: ]
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PubMed id
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Abstract
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The spread of antibiotic resistant bacteria is a global threat that shakes the
foundations of modern healthcare. β-Lactamases are enzymes that confer
resistance to β-lactam antibiotics in bacteria, and there is a critical need
for new inhibitors of these enzymes for combination therapy together with an
antibiotic. With this in mind, we have screened a library of 490 fragments to
identify starting points for the development of new inhibitors of the class D
β-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR),
dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have
uncovered structure-activity relationships and used alternate conformations from
a crystallographic structure to grow a fragment into a more potent compound with
a KD of 50 μM and an IC50 of 18 μM.
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