1. IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach
- Author
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Mariana S.A. Silva, Ederlan de Souza Ferreira, Carolina Oliveira de Souza, Eduardo Maffud Cilli, Caio Alexandre da Cruz Souza, Jaff Ribeiro da Silva, Francine Johansson Azeredo, Marcelo Santos Castilho, Johnnie Santos, Victória Souza, Biane Oliveira Philadelpho, Victória Santiago, Universidade Federal da Bahia (UFBA), and Universidade Estadual Paulista (UNESP)
- Subjects
Simvastatin ,Statin ,QH301-705.5 ,medicine.drug_class ,cowpea peptides ,In silico ,Reductase ,Article ,Catalysis ,Inorganic Chemistry ,Catalytic Domain ,Cowpea peptides ,medicine ,Animals ,Amino Acid Sequence ,Biology (General) ,Physical and Theoretical Chemistry ,Binding site ,QD1-999 ,Molecular Biology ,Spectroscopy ,Plant Proteins ,Pharmacokinetic properties ,Binding Sites ,biology ,Chemistry ,Vigna ,Organic Chemistry ,Substrate (chemistry) ,Hydrogen Bonding ,molecular docking ,General Medicine ,In vitro ,Computer Science Applications ,Molecular Docking Simulation ,Biochemistry ,Molecular docking ,HMG-CoA reductase ,biology.protein ,competitive HMG-CoA reductase inhibitor ,Hydroxymethylglutaryl CoA Reductases ,Competitive HMG-CoA reductase inhibitor ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,pharmacokinetic properties ,Peptides ,Half-Life ,medicine.drug - Abstract
In this study, in silico approaches are employed to investigate the binding mechanism of peptides derived from cowpea β-vignin and HMG-CoA reductase. With the obtained information, we designed synthetic peptides to evaluate their in vitro enzyme inhibitory activity. In vitro, the total protein extract and <, 3 kDa fraction, at 5000 µg, support this hypothesis (95% and 90% inhibition of HMG-CoA reductase, respectively). Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides were predicted to bind to the substrate binding site of HMGCR via HMG-CoAR. In silico, it was established that the mechanism of HMG-CoA reductase inhibition largely entailed mimicking the interactions of the decalin ring of simvastatin and via H-bonding, in vitro studies corroborated the predictions, whereby the HMG-CoA reductase activity was decreased by 69%, 77%, and 78%, respectively. Our results suggest that Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides derived from cowpea β-vignin have the potential to lower cholesterol synthesis through a statin-like regulation mechanism.
- Published
- 2021