title: 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.
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real Hernandez
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: edemejia@illinois.edu.
authors.forename: Elvira
authors.initials: E
authors.lastname: Gonzalez de Mejia
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D003198:Computer Simulation; D020895:Enterocytes / Q000737:chemistry / Q000378:metabolism; D000069438:Ezetimibe / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018532:Pisum sativum / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D027805:Phaseolus / Q000737:chemistry; D011485:Protein Binding
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010455:Peptides; D002784:Cholesterol; D000069438:Ezetimibe
keywords: AutoDock Vina; Bean peptides; Black beans; Cholesterol absorption; NPC1L1