6V1P

Structure of VIM-2 bound to QPX7728 at 1.20 A

6V1P の概要

• エントリーDOI: 10.2210/pdb6v1p/pdb
• 分子名称: Beta-lactamase class B VIM-2, (1~{a}~{R},7~{b}~{S})-5-fluoranyl-2,2-bis(oxidanyl)-1~{a},7~{b}-dihydro-1~{H}-cyclopropa[c][1,2]benzoxaborinine-4-carboxylic acid, ZINC ION, ... (6 entities in total)
• 機能のキーワード: carbapenemase, boronate, inhibitor, beta-lactamase, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52677.76

構造登録者

Pemberton, O.A.,Chen, Y. (登録日: 2019-11-20, 公開日: 2020-03-25, 最終更新日: 2023-10-11)

主引用文献

Hecker, S.J.,Reddy, K.R.,Lomovskaya, O.,Griffith, D.C.,Rubio-Aparicio, D.,Nelson, K.,Tsivkovski, R.,Sun, D.,Sabet, M.,Tarazi, Z.,Parkinson, J.,Totrov, M.,Boyer, S.H.,Glinka, T.W.,Pemberton, O.A.,Chen, Y.,Dudley, M.N.
Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-beta-lactamases.
J.Med.Chem., 63:7491-7507, 2020

PubMed Abstract: Despite major advances in the β-lactamase inhibitor field, certain enzymes remain refractory to inhibition by agents recently introduced. Most important among these are the class B (metallo) enzyme NDM-1 of Enterobacteriaceae and the class D (OXA) enzymes of . Continuing the boronic acid program that led to vaborbactam, efforts were directed toward expanding the spectrum to allow treatment of a wider range of organisms. Through key structural modifications of a bicyclic lead, stepwise gains in spectrum of inhibition were achieved, ultimately resulting in QPX7728 (). This compound displays a remarkably broad spectrum of inhibition, including class B and class D enzymes, and is little affected by porin modifications and efflux. Compound is a promising agent for use in combination with a β-lactam antibiotic for the treatment of a wide range of multidrug resistant Gram-negative bacterial infections, by both intravenous and oral administration.

PubMed: 32150407
DOI: 10.1021/acs.jmedchem.9b01976

実験手法

X-RAY DIFFRACTION (1.2 Å)