Identification and in silico characterization of a novel peptide inhibitor of angiotensin converting enzyme from pigeon pea (Cajanus cajan)

• Published in: Phytomedicine (Stuttgart) 2017-12, Vol.36, p.1-7
• Main Authors: Nawaz, K.A. Ayub, David, Swapna Merlin, Murugesh, Easwaran, Thandeeswaran, Murugesan, Kiran, Kalarikkal Gopikrishnan, Mahendran, Ramasamy, Palaniswamy, Muthusamy, Angayarkanni, Jayaraman
• Format: Article
• Language: English
• Subjects: Angiotensin converting enzyme; Angiotensin-Converting Enzyme Inhibitors - chemistry; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Aspergillus niger - metabolism; Cajanus - chemistry; Cajanus - metabolism; Catalytic Domain; Chromatography, Gel; Computer Simulation; Drug Evaluation, Preclinical - methods; Humans; Inhibitor; Molecular docking; Molecular Docking Simulation; Molecular Weight; Peptide; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - metabolism; Purification; Tandem Mass Spectrometry
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.09.013

Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases. Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives. The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension. Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking. The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver–Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE. The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases. [Display omitted]