title: Evaluating molecular mechanism of hypotensive peptides interactions with renin and angiotensin converting enzyme.
abstract: Our previous study showed that three rapeseed protein-derived peptides (TF, LY and RALP) inhibited the in vitro activities of angiotensin converting enzyme (ACE) and renin. Oral administration of these peptides to spontaneously hypertensive rats led to reductions in systolic blood pressure. In the present work, we examined the potential molecular mechanisms responsible for the ACE- and renin-inhibitory activities of these peptides. Enzyme inhibition kinetics showed competitive, non-competitive and mixed-type peptide-dependent inhibition of renin and ACE activities. Intrinsic fluorescence intensity data showed that LY and RALP have stronger binding effects on ACE molecule compared to that of TF. LY and RALP showed the highest inhibition of ACE and renin activities, respectively. Circular dichroism data showed that the inhibitory mechanism involved extensive peptide-dependent reductions in α-helix and β-sheet fractions of ACE and renin protein conformations. Molecular docking studies confirmed that the higher renin-inhibitory activity of RALP may be due to formation of several hydrogen bonds (H-bonds) with the enzyme's active site residues. The rapeseed peptides inhibited renin and ACE activities mostly through binding to enzyme active site or non-active sites and forming extensive H-bonds that distorted the normal configuration required for catalysis. Data presented from this work could enhance development of highly potent antihypertensive natural peptides or peptidomimetics.
authors.affiliation: College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, People's Republic of China; The School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China; Department of Human Nutritional Sciences and the Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Human Nutritional Sciences and the Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Rotimi E
authors.initials: RE
authors.lastname: Aluko
authors.affiliation: College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, People's Republic of China; The School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Xing-Rong
authors.initials: XR
authors.lastname: Ju
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D055162:Biocatalysis / Q000187:drug effects; D020134:Catalytic Domain; D002942:Circular Dichroism; D007700:Kinetics; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011918:Rats, Inbred SHR; D012083:Renin / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D000092502:Renin Inhibitors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010455:Peptides; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000092502:Renin Inhibitors