Kinetic Profile and Molecular Dynamic Studies Show that Y229W Substitution in an NDM-1/L209F Variant Restores the Hydrolytic Activity of the Enzyme toward Penicillins, Cephalosporins, and Carbapenems.
Amino Acid Substitution
/ drug effects
Anti-Bacterial Agents
/ pharmacology
Carbapenems
/ pharmacology
Catalytic Domain
/ drug effects
Cephalosporins
/ pharmacology
Hydrolysis
/ drug effects
Kinetics
Microbial Sensitivity Tests
/ methods
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
/ methods
Mutation
/ drug effects
Penicillins
/ pharmacology
beta-Lactamases
/ genetics
NDM
enzyme kinetics
metallo-β-lactamases
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
27
10
2018
accepted:
23
01
2019
entrez:
29
3
2019
pubmed:
29
3
2019
medline:
27
2
2020
Statut:
epublish
Résumé
The New Delhi metallo-β-lactamase-1 (NDM-1) enzyme is the most common metallo-β-lactamase identified in many Gram-negative bacteria causing severe nosocomial infections. The aim of this study was to focus the attention on non-active-site residues L209 and Y229 of NDM-1 and to investigate their role in the catalytic mechanism. Specifically, the effect of the Y229W substitution in the L209F variant was evaluated by antimicrobial susceptibility testing, kinetic, and molecular dynamic (MD) studies. The Y229W single mutant and L209F-Y229W double mutant were generated by site-directed mutagenesis. The
Identifiants
pubmed: 30917978
pii: AAC.02270-18
doi: 10.1128/AAC.02270-18
pmc: PMC6437508
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Carbapenems
0
Cephalosporins
0
Penicillins
0
beta-Lactamases
EC 3.5.2.6
beta-lactamase NDM-1
EC 3.5.2.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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