Bean peptides have higher in silico binding affinities than ezetimibe for the N-terminal domain of cholesterol receptor Niemann-Pick C1 Like-1

Abstract

Niemann-Pick C1 like-1 (NPC1L1) mediates cholesterol absorption at the apical membrane of enterocytes through a yet unknown mechanism. Bean, pea, and lentil proteins are naturally hydrolyzed during digestion to produce peptides. The potential for pulse peptides to have high binding affinities for NPC1L1 has not been determined. In this study , in silico binding affinities and interactions were determined between the N-terminal domain of NPC1L1 and 14 pulse peptides (5≥ amino acids) derived through pepsin-pancreatin digestion. Peptides were docked in triplicate to the N-terminal domain using docking program AutoDock Vina, and results were compared to those of ezetimibe, a prescribed NPC1L1 inhibitor. Three black bean peptides (-7.2 to -7.0kcal/mol) and the cowpea bean dipeptide Lys-Asp (-7.0kcal/mol) had higher binding affinities than ezetimibe (-6.6kcal/mol) for the N-terminal domain of NPC1L1. Lentil and pea peptides studied did not have high binding affinities. The common bean peptide Tyr-Ala-Ala-Ala-Thr (-7.2kcal/mol), which can be produced from black or navy bean proteins, had the highest binding affinity. Ezetimibe and peptides with high binding affinities for the N-terminal domain are expected to interact at different locations of the N-terminal domain. All high affinity black bean peptides are expected to have van der Waals interactions with SER130, PHE136, and LEU236 and a conventional hydrogen bond with GLU238 of NPC1L1. Due to their high affinity for the N-terminal domain of NPC1L1, black and cowpea bean peptides produced in the digestive track have the potential to disrupt interactions between NPC1L1 and membrane proteins that lead to cholesterol absorption.

Bioactive Peptides

“…Peptides in rice bran protein hydrolysates were also found to inhibit cholesterol micellar solubilization and may be important in reducing cholesterol [19]. In a recent study, Hernandez et al [110] observed that black bean and cowpea derived peptide YAAAT could tightly bind to the N -terminal domain of Niemann-Pick C1 (NPC1L1) to disrupt interactions between NPC1L1 and membrane proteins to enhance cholesterol absorption. Duranti et al [111] also observed that consumption of the α′ subunit reduced plasma cholesterol levels by 36% and also upregulated liver β-very low density lipoprotein cholesterol receptors in rats.…”

Manufacturing of Plant-Based Bioactive Peptides Using Enzymatic Methods to Meet Health and Sustainability Targets of the Sustainable Development Goals

“…Therefore, there is an increasing demand in sourcing natural and food-based alternatives of these drugs. Hypocholesterolemic activity has been observed in some plant-based biopeptides, including ones from rice bran (Zhang et al, 2012), cowpea (Marques et al, 2015;Hernandez and de Mejia, 2017), cumin seed (Siow et al, 2016), and soy (Duranti et al, 2004;Lammi et al, 2015). Recently, Coelho et al (2018) hydrolysed chia seed protein into biopeptides using Alcalase and Flavourzyme.…”

Legumes as Functional Food for Cardiovascular Disease

“…NPC1L1 is involved in the cholesterol absorption at the apical membrane of enterocytes through an unknown mechanism. The cowpea KD dipeptide and three black bean pea peptides (YAAAT, ERAF, and FATGT) were found in silico to have binding affinities to the N-terminal domain of NPC1L1 and were opined to have great potential to disrupt the interaction between NPC1L1 and membrane proteins facilitating cholesterol absorption better than Ezetimibe [325].…”