7AYJ

Metallo beta-lactamse Vim-1 with a sulfamoyl inhibitor.

7AYJ の概要

• エントリーDOI: 10.2210/pdb7ayj/pdb
• 分子名称: Beta-lactamase VIM-1, ZINC ION, 3-(4-fluorophenyl)-1-sulfamoyl-pyrrole-2-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: vim1, metallo beta lactamse, inhibition, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27345.84

構造登録者

Farley, A.J.M.,Ermolovich, I.,Calvopina, K.,Rabe, P.,Brem, J.,Schofield, C.J. (登録日: 2020-11-12, 公開日: 2021-05-12, 最終更新日: 2024-11-20)

主引用文献

Farley, A.J.M.,Ermolovich, Y.,Calvopina, K.,Rabe, P.,Panduwawala, T.,Brem, J.,Bjorkling, F.,Schofield, C.J.
Structural Basis of Metallo-beta-lactamase Inhibition by N -Sulfamoylpyrrole-2-carboxylates.
Acs Infect Dis., 7:1809-1817, 2021

PubMed Abstract: Metallo-β-lactamases (MBLs) can efficiently catalyze the hydrolysis of all classes of β-lactam antibiotics except monobactams. While serine-β-lactamase (SBL) inhibitors (e.g., clavulanic acid, avibactam) are established for clinical use, no such MBL inhibitors are available. We report on the synthesis and mechanism of inhibition of -sulfamoylpyrrole-2-carboxylates (NSPCs) which are potent inhibitors of clinically relevant B1 subclass MBLs, including NDM-1. Crystallography reveals that the -sulfamoyl NH group displaces the dizinc bridging hydroxide/water of the B1 MBLs. Comparison of crystal structures of an NSPC and taniborbactam (VRNX-5133), presently in Phase III clinical trials, shows similar binding modes for the NSPC and the cyclic boronate ring systems. The presence of an NSPC restores meropenem efficacy in clinically derived and NDM-1. The results support the potential of NSPCs and related compounds as efficient MBL inhibitors, though further optimization is required for their clinical development.

PubMed: 34003651
DOI: 10.1021/acsinfecdis.1c00104

実験手法

X-RAY DIFFRACTION (1.21 Å)