5VFD
Diazabicyclooctenone ETX2514 bound to Class D beta lactamase OXA-24 from A. baumannii
Summary for 5VFD
| Entry DOI | 10.2210/pdb5vfd/pdb |
| Descriptor | Beta-lactamase, SULFATE ION, (2S,5R)-1-formyl-4-methyl-5-[(sulfooxy)amino]-1,2,5,6-tetrahydropyridine-2-carboxamide, ... (5 entities in total) |
| Functional Keywords | etx2514, beta-lactamase, pbp gram negative, astrazeneca, entasis, a. baumannii, covalent inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 1 |
| Total formula weight | 28623.50 |
| Authors | Olivier, N.B.,Lahiri, S. (deposition date: 2017-04-07, release date: 2017-06-07, Last modification date: 2025-03-26) |
| Primary citation | Durand-Reville, T.F.,Guler, S.,Comita-Prevoir, J.,Chen, B.,Bifulco, N.,Huynh, H.,Lahiri, S.,Shapiro, A.B.,McLeod, S.M.,Carter, N.M.,Moussa, S.H.,Velez-Vega, C.,Olivier, N.B.,McLaughlin, R.,Gao, N.,Thresher, J.,Palmer, T.,Andrews, B.,Giacobbe, R.A.,Newman, J.V.,Ehmann, D.E.,de Jonge, B.,O'Donnell, J.,Mueller, J.P.,Tommasi, R.A.,Miller, A.A. ETX2514 is a broad-spectrum beta-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including Acinetobacter baumannii. Nat Microbiol, 2:17104-17104, 2017 Cited by PubMed Abstract: Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of β-lactamases, enzymes that inactivate β-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new β-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii. This report describes the rational design and characterization of expanded-spectrum serine β-lactamase inhibitors that potently inhibit clinically relevant class A, C and D β-lactamases and penicillin-binding proteins, resulting in intrinsic antibacterial activity against Enterobacteriaceae and restoration of β-lactam activity in a broad range of MDR Gram-negative pathogens. One of the most promising combinations is sulbactam-ETX2514, whose potent antibacterial activity, in vivo efficacy against MDR A. baumannii infections and promising preclinical safety demonstrate its potential to address this significant unmet medical need. PubMed: 28665414DOI: 10.1038/nmicrobiol.2017.104 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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