5DTT
Fragments bound to the OXA-48 beta-lactamase: Compound 3
Summary for 5DTT
| Entry DOI | 10.2210/pdb5dtt/pdb |
| Related | 5DTS |
| Descriptor | Beta-lactamase, CHLORIDE ION, 3-(1,3-thiazol-2-yl)benzoic acid, ... (5 entities in total) |
| Functional Keywords | inhibitor, complex, fragment, lactamase, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 4 |
| Total formula weight | 113735.56 |
| 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 Cited by 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: 27165692DOI: 10.1021/acs.jmedchem.6b00660 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.10000527 Å) |
Structure validation
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