5DTS

Fragments bound to the OXA-48 beta-lactamase: Compound 2

Summary for 5DTS

• Entry DOI: 10.2210/pdb5dts/pdb
• Related: 5DVA
• Descriptor: Beta-lactamase, 3-(pyridin-3-yl)benzoic acid, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, fragment, lactamase, hydrolase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 4
• Total formula weight: 114059.84

Authors

Lund, B.A.,Christopeit, T.,Leiros, H.-K.S. (deposition date: 2015-09-18, release date: 2016-05-25, Last modification date: 2024-01-10)

Primary citation

Lund, B.A.,Christopeit, T.,Guttormsen, Y.,Bayer, A.,Leiros, H.K.
Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.
J.Med.Chem., 59:5542-5554, 2016

PubMed Abstract: 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.

PubMed: 27165692
DOI: 10.1021/acs.jmedchem.6b00660

Experimental method

X-RAY DIFFRACTION (1.94015871727 Å)