Cholesterol-lowering drugs the simvastatin and atorvastatin change the protease activity of pepsin: An experimental and computational study

• Published in: International journal of biological macromolecules 2021-01, Vol.167, p.1414-1423
• Main Authors: Shahlaei, Mohsen, Zamani, Paria, Farhadian, Negin, Balaei, Fatemeh, Ansari, Mohabbat, Moradi, Sajad
• Format: Article
• Language: English
• Subjects: Anticholesteremic Agents - chemistry; Atorvastatin; Atorvastatin - chemistry; Binding Sites; Catalysis; Catalytic Domain; Enzyme activity; Fluorescence; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Molecular Docking Simulation; Molecular dynamics simulation; Molecular Structure; Pepsin; Pepsin A - chemistry; Pharmaceutical Preparations - chemistry; Protein Binding; Proteolysis; Simvastatin; Simvastatin - chemistry; Spectrometry, Fluorescence; Spectrophotometry; Spectroscopy study; Spectroscopy, Fourier Transform Infrared; Thermodynamics
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.11.095

In this study, the effect of long-term use drugs of cholesterol-lowering atorvastatin and simvastatin on the activity and molecular structure of pepsin as important gastric enzyme was investigated by various experimental and computational methods. Based on the results obtained from fluorescence experiments, both drugs can bond to pepsin and quench the fluorescence intensity of protein through the static quenching mechanism. Also analysis of the thermodynamic parameters of binding the drugs to pepsin showed that the main forces in the complex formation for both are hydrophobic interactions and van der Waals forces. The effects of the drugs on the enzymatic activity of pepsin were then investigated and results showed that in the presence of both drugs the catalytic activity of the enzyme was significantly increased in lower (0.3–0.6 mM) concentrations however about the atorvastatin, increasing the concentration (0.9 mM) decreased the protease activity of pepsin. Also as a result of the FTIR studies, it was found that binding of the drugs to protein did not significant alteration in the structure of the protein. In order to obtain the atomic details of drug-protein interactions, the computational calculations were performed. The results in good agreement with those obtained from the experimental for interaction; confirm that the drugs both are bind to a cleft near the active site of the protein without any change in the structure of pepsin. Overall from the results obtained in this study, it can be concluded that both simvastatin and atorvastatin can strongly bond to a location close to the active site of pepsin and the binding change the enzymatic activity of protein.