5VFD

Diazabicyclooctenone ETX2514 bound to Class D beta lactamase OXA-24 from A. baumannii

5VFD の概要

• エントリーDOI: 10.2210/pdb5vfd/pdb
• 分子名称: Beta-lactamase, SULFATE ION, (2S,5R)-1-formyl-4-methyl-5-[(sulfooxy)amino]-1,2,5,6-tetrahydropyridine-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: etx2514, beta-lactamase, pbp gram negative, astrazeneca, entasis, a. baumannii, covalent inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28623.50

構造登録者

Olivier, N.B.,Lahiri, S. (登録日: 2017-04-07, 公開日: 2017-06-07, 最終更新日: 2025-03-26)

主引用文献

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

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: 28665414
DOI: 10.1038/nmicrobiol.2017.104

実験手法

X-RAY DIFFRACTION (1.93 Å)