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Structural insight into the binding mode of cefotaxime and meropenem to TEM-1, SHV-1, KPC-2, and Amp-C type beta-lactamases.
- Source :
-
Cell biochemistry and biophysics [Cell Biochem Biophys] 2024 Jun; Vol. 82 (2), pp. 1299-1308. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
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 (K <subscript>m</subscript> ) 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 (K <subscript>b</subscript> ) values are 10 <superscript>4</superscript> , 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.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Binding Sites
Kinetics
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents metabolism
Hydrogen Bonding
Thienamycins chemistry
Thienamycins metabolism
Bacterial Proteins metabolism
Bacterial Proteins chemistry
Meropenem chemistry
Meropenem pharmacology
Meropenem metabolism
Cefotaxime chemistry
Cefotaxime metabolism
Cefotaxime pharmacology
beta-Lactamases chemistry
beta-Lactamases metabolism
Molecular Dynamics Simulation
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0283
- Volume :
- 82
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 38730202
- Full Text :
- https://doi.org/10.1007/s12013-024-01284-y