Structural insight into the binding mode of cefotaxime and meropenem to TEM-1, SHV-1, KPC-2, and Amp-C type beta-lactamases.
Cell Biochem Biophys
; 82(2): 1299-1308, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38730202
ABSTRACT
Antimicrobial resistance is an emerging threat to public health around the world. The study employs computational and biophysical methods to investigate the properties of cefotaxime and meropenem's binding to various beta-lactamases like TEM-1, SHV-1, KPC-2, and Amp-C. The enzyme kinetics of purified proteins revealed an increase in Michaelis constant (Km) value in the presence of meropenem and cefotaxime, indicating a decrease in enzyme affinity for nitrocefin. Proteins interact with meropenem/cefotaxime, causing quenching through complex formation. All proteins have one binding site, and binding constant (Kb) values are 104, indicating strong interaction. The study found that meropenem and cefotaxime had high fitness scores for Amp-C, KPC-2,TEM-1 and SHV-1, with binding energy ranging from -7.4 to -7.8, and hydrogen bonds between them. Molecular Dynamic simulation of protein-ligand complexes revealed cefotaxime-binding proteins have slightly lower Root Mean Square Deviation(RMSD) than meropenem-binding proteins, indicating stable association antibiotics with these proteins.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Unión Proteica
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Beta-Lactamasas
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Cefotaxima
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Simulación de Dinámica Molecular
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Meropenem
Idioma:
En
Revista:
Cell Biochem Biophys
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Estados Unidos