In vitro and in silico studies of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitory activity of the cowpea Gln-Asp-Phe peptide

• Published in: Food chemistry Vol. 259; pp. 270 - 277
• Main Authors: Silva, Mariana Barros de Cerqueira e, Souza, Caio Alexandre da Cruz, Philadelpho, Biane Oliveira, Cunha, Mariana Mota Novais da, Batista, Fabiana Pacheco Reis, Silva, Jaff Ribeiro da, Druzian, Janice Izabel, Castilho, Marcelo Santos, Cilli, Eduardo Maffud, Ferreira, Ederlan S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2018
• Subjects: Concentration-response effect; HMG-CoA reductase inhibitor; Peptide bioactive; β-Vignin protein; β-Vignin protein; Peptide bioactive; HMG-CoA reductase inhibitor; Concentration-response effect
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2018.03.132

•In silico prediction of peptide capable of interacting with the HMG-CoA reductase.•In vitro experiments showed that the <3 kDa peptide inhibits HMG-CoA reductase activity.•The tripeptide QDF inhibits HMG-CoA reductase in a dose-dependent manner.•In silico studies show the binding profile of QDF and their molecular interactions.
Previous studies have shown that cowpea protein positively interferes with cholesterol metabolism. In this study, we evaluated the ability of the fraction containing peptides of <3 kDa, as well as that of the Gln-Asp-Phe (QDF) peptide, derived from cowpea β-vignin protein, to inhibit HMG-CoA reductase activity. We established isolation and chromatography procedures to effectively obtain the protein with a purity above 95%. In silico predictions were performed to identify peptide sequences capable of interacting with HMG-CoA reductase. In vitro experiments showed that the fraction containing peptides of <3 kDa displayed inhibition of HMG-CoA reductase activity. The tripeptide QDF inhibits HMG-CoA reductase (IC50 = 12.8 μM) in a dose-dependent manner. Furthermore, in silico studies revealed the binding profile of the QDF peptide and hinted at the molecular interactions that are responsible for its activity. Therefore, this study shows, for the first time, a peptide from cowpea β-vignin protein that inhibits HMG-CoA reductase and the chemical modifications that should be investigated to evaluate its binding profile.