Spectroscopic and biochemical characterization of metallo-ß-lactamase IMP-1 with dicarboxylic, sulfonyl, and thiol inhibitors.
Bioorg Med Chem
; 40: 116183, 2021 06 15.
Article
em En
| MEDLINE
| ID: mdl-33965839
ABSTRACT
In an effort to probe the biophysical mechanisms of inhibition for ten previously-reported inhibitors of metallo-ß-lactamases (MBL) with MBL IMP-1, equilibrium dialysis, metal analyses coupled with atomic absorption spectroscopy (AAS), native state mass spectrometry (native MS), and ultraviolet-visible spectrophotometry (UV-VIS) were used. 6-(1H-tetrazol-5-yl) picolinic acid (1T5PA), ANT431, D/l-captopril, thiorphan, and tiopronin were shown to form IMP-1/Zn(II)/inhibitor ternary complexes, while dipicolinic acid (DPA) and 4-(3-aminophenyl)pyridine-2,6-dicarboxylic acid (3AP-DPA) stripped some metal from the active site of IMP but also formed ternary complexes. DPA and 3AP-DPA stripped less metal from IMP-1 than from VIM-2 but stripped more metal from IMP-1 than from NDM-1. In contrast to a previous report, pterostilbene does not appear to bind to IMP-1 under our conditions. These results, along with previous studies, demonstrate similar mechanisms of inhibition toward different MBLs for different MBL inhibitors.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfidrila
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Sulfetos
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Beta-Lactamases
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Ácidos Dicarboxílicos
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Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos