Novel ACE inhibitory peptides from enzymatic hydrolysate of Channa punctata protein: In vitro and In silico assay of structure-activity relationship

Abstract

Channa punctata flesh meat is well known for its ethnomedicinal values. The objective of this study was to isolate and identify peptides having Angiotensin-Converting Enzyme (ACE) inhibitory potential from the Channa punctata fish protein hydrolysates (FPH) and to investigate the inhibitory mechanism by docking study. ACE inhibitory potential of the ultrafiltrate of C. punctata 240 min protein hydrolysates was analysed. The PrAHyd240 (<3 kDa) had the strongest ACE inhibitory potential as it has the lowest IC50 value i.e., 66.08 μg/ml. To identify the ACE inhibitory peptides, PrAHyd240 (<3 kDa) was evaluated by LC ESI mass spectrometer. The amino acid residues of 3 peptides within the intensity count 100–250 were determined by de novo sequencing.The docking analysis reveals that the peptides were deeply buried in the active site of ACE. Thr 5 of ISISTSGGSFR, Val 3 of SLVNLGGSK, and Val 6, Ala 7 of SISISVAR form highly stable metal coordination bonds with the Zn cofactor present in the binding site of ACE. Similar to captopril, the peptide SISISVAR interacted with the amino acids His 353 and His 513 of the binding sites of ACE via H-bond interactions. The MD simulation study reveals that the peptides ISISTSGGSFR, SLVNLGGSK, and SISISVAR interacted with the Zn+ ion via H-bond with 100% occupancy respectively. The above study reveals that Channa punctata protein hydrolysate is a rich source of ACE inhibitory peptides and the isolated peptides ISISTSGGSFR, SLVNLGGSK, and SISISVAR are potential ingredients in the preparation of functional foods.