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IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach
- Source :
- International Journal of Molecular Sciences, Scopus, Repositório Institucional da UNESP, Universidade Estadual Paulista (UNESP), instacron:UNESP, International Journal of Molecular Sciences, Vol 22, Iss 11067, p 11067 (2021), Volume 22, Issue 20
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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 &lt<br />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<br />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.
- 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
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....3482e92b5851405bcfb504a7ad33d3d6