期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 210, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2020.111123
关键词
VIM-2; NDM-1; Antibiotic resistance; Metallo-beta-lactamase; Mechanism of inhibition; Native state ESI-MS
资金
- National Institutes of Health [R15GM134454, GM111926]
To probe the mechanism of inhibition of several previously-published metallo-beta-lactamase (MBL) inhibitors for the clinically-important MBL Verona integron-encoded metallo-beta-lactamase 2 (VIM-2), equilibrium dialyses with metal analyses, native state electrospray ionization mass spectrometry (ESI-MS), and UV-Vis spectrophotometry were utilized. The mechanisms of inhibition were analyzed for ethylenediaminetetraacetic acid (EDTA); dipicolinic acid (DPA) and DPA analogs 6-(1H-tetrazol-5-yl)picolinic acid (1T5PA) and 4-(3-aminophenyl)pyridine-2,6-dicarboxylic acid (3AP-DPA); thiol-containing compounds, 2,3-dimercaprol, thiorphan, captopril, and tiopronin; and 5-(pyridine-3-sulfonamido)-1,3-thiazole-4-carboxylic acid (ANT-431). UV-Vis spectroscopy and native-state ESI-MS results showed the formation of ternary complexes between VIM-2 and 1T5PA, ANT-431, thiorphan, captopril, and tiopronin, while a metal stripping mechanism was shown with VIM-2 and EDTA and DPA. The same approaches were used to show the formation of a ternary complex between New Delhi Metallo-beta-lactamase (NDM-1) and ANT-431. The studies presented herein show that most of the inhibitors utilize a similar mechanism of inhibition as previously reported for NDM-1. These studies also demonstrate that native mass spectrometry can be used to probe the mechanism of inhibition at lower enzyme/inhibitor concentrations than has previously been achieved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据