title: Isolation, purification and molecular mechanism of a peanut protein-derived ACE-inhibitory peptide.
abstract: Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension.
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Shi
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Applied Sciences, RMIT University, City Campus, Melbourne, Australia.
authors.forename: Benu
authors.initials: B
authors.lastname: Adhikari
mesh_terms: D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010367:Arachis / Q000737:chemistry*; D001665:Binding Sites; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009842:Oligopeptides; D010940:Plant Proteins; D007703:Peptidyl-Dipeptidase A