Probing the interaction of l‐captopril with metallo‐β‐lactamase CcrA by fluorescence spectra and molecular dynamic simulation |
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Authors: | Penghui Shi Yan Zhang Yuhua Li Liujiao Bian |
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Affiliation: | College of Life Science, Northwest University, Xi'an, Shaanxi, People's Republic of China |
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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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Keywords: | fluorescence l‐captopril metallo‐β ‐lactamase molecular dynamic molecular recognition |
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