1. In vitro and in silico studies of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitory activity of the cowpea Gln-Asp-Phe peptide.
- Author
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Silva MBCE, Souza CADC, Philadelpho BO, Cunha MMND, Batista FPR, Silva JRD, Druzian JI, Castilho MS, Cilli EM, and Ferreira ES
- Subjects
- Amino Acid Sequence, Binding Sites, Catalytic Domain, Chromatography, High Pressure Liquid, Chromatography, Reverse-Phase, Humans, Hydroxymethylglutaryl CoA Reductases chemistry, Hydroxymethylglutaryl-CoA Reductase Inhibitors chemistry, Molecular Docking Simulation, Peptides analysis, Peptides chemistry, Hydroxymethylglutaryl CoA Reductases metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors metabolism, Peptides metabolism, Vigna metabolism
- Abstract
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 (IC
50 = 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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