Angiotensin Converting Enzyme (ACE)-Peptide Interactions: Inhibition Kinetics, In Silico Molecular Docking and Stability Study of Three Novel Peptides Generated from Palm Kernel Cake Proteins

• Main Authors: Mohammad Zarei, Najib Bin Zainal Abidin, Shehu Muhammad Auwal, Shyan Yea Chay, Zaibunnisa Abdul Haiyee, Adi Md Sikin, Nazamid Saari
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Biomolecules
• Subjects: peptide; kinetics; molecular docking; angiotensin converting enzyme inhibitory activity
• Online Access: https://www.mdpi.com/2218-273X/9/10/569

Three novel peptide sequences identified from palm kernel cake (PKC) generated protein hydrolysate including YLLLK, WAFS and GVQEGAGHYALL were used for stability study against angiotensin-converting enzyme (ACE), ACE-inhibition kinetics and molecular docking studies. Results showed that the peptides were degraded at different cleavage degrees of 94%, 67% and 97% for YLLLK, WAFS and GVQEGAGHYALL, respectively, after 3 h of incubation with ACE. YLLLK was found to be the least stable (decreased ACE-inhibitory activity) compared to WAFS and GVQEGAGHYALL (increased ACE-inhibitory activity). YLLLK showed the lowest K_i (1.51 mM) in inhibition kinetics study when compared to WAFS and GVQEGAGHYALL with K_i of 2 mM and 3.18 mM, respectively. In addition, ACE revealed the lowest <inline-formula> <math display="inline"> <semantics> <mrow> <msubsup> <mi>K</mi> <mi mathvariant="normal">m</mi> <mrow> <mi>app</mi> </mrow> </msubsup> </mrow> </semantics> </math> </inline-formula> and <inline-formula> <math display="inline"> <semantics> <mrow> <msubsup> <mi>V</mi> <mrow> <mi>max</mi> </mrow> <mrow> <mi>app</mi> </mrow> </msubsup> </mrow> </semantics> </math> </inline-formula> and higher catalytic efficiency (CE) in the presence of YLLLK at different concentrations, implying that the enzyme catalysis decreased and hence the inhibition mode increased. Furthermore, YLLLK showed the lowest docking score of −8.224 and seven interactions with tACE, while peptide GVQEGAGHYALL showed the higher docking score of −7.006 and five interactions with tACE.