Probing the interaction of l-captopril with metallo-β-lactamase CcrA by fluorescence spectra and molecular dynamic simulation

Luminescence : the Journal of Biological and Chemical Luminescence
Penghui ShiLiujiao Bian

Abstract

Both the molecular recognition and interaction of metallo-β-lactamase CcrA with l-captopril were studied by the combined use of fluorescence spectra and molecular dynamic simulation. The results showed that the binding constant was 8.89 × 104  L mol-1 at 296 K. Both Zn1 and Zn2 displayed tetrahedral coordination geometries in the CcrA-Lcap complex, the S atom in l-captopril displaced the nucleophilic hydroxide in apo CcrA and occupied the fourth coordination site for each ion, resulting in a competitively inhibited CcrA enzyme. Strong electrostatic interaction between the two zinc ions in CcrA and negatively charged l-captopril provided the main driving force for the binding affinity. Through a partly structural transformation from β-sheet to random coil, loop 1 (residues 24-34) completely opened the binding pocket of CcrA to allow an induced fit of the newly introduced ligand. This study may provide some valuable information for designing and developing a more tightly binding inhibitor to resist superbugs.

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Citations

Dec 6, 2018·Physical Chemistry Chemical Physics : PCCP·Deliang ChenXiaolin Fan
Sep 14, 2019·Journal of Biomolecular Structure & Dynamics·Bhavya Somalapura GangadharappaTeja Priya Vardhineni

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