Characterization of ACE Inhibitory Peptides from Mactra veneriformis Hydrolysate by Nano-Liquid Chromatography Electrospray Ionization Mass Spectrometry (Nano-LC-ESI-MS) and Molecular Docking

Abstract

Food-derived bioactive compounds are gaining increasing significance in life sciences. In the present study, we identified angiotensin I-converting enzyme (ACE)-inhibitory peptides from Mactra veneriformis hydrolysate using a nano-LC-MS/MS method. Mactra veneriformis hydrolysate was first separated into four fractions (F1–F4) based on molecular weight by ultrafiltration. The fraction with molecular weight lower than 1 kDa (F1) showed the highest ACE inhibitory activity. F1 was then analyzed by a high throughput nano-LC-MS/MS method and sequences of peptides in F1 were calculated accordingly. The 27 peptides identified as above were chemically synthesized and tested for ACE-inhibitory activity. The hexapeptide VVCVPW showed the highest potency with an IC50 value of 4.07 μM. We then investigated the interaction mechanism between the six most potent peptides and ACE by molecular docking. Our docking results suggested that the ACE inhibitory peptides bind to ACE via interactions with His383, His387, and Glu411 residues. Particularly, similar to the thiol group of captopril, the cysteine thiol group of the most potent peptide VVCVPW may play a key role in the binding of this peptide to the ACE active site.

Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure–Activity Relationship

“…These results indicate that the ACE active binding sites of different peptides are not identical. This conclusion is consistent with the observations of Liu et al [ 35 ]. Overall, our molecular docking studies indicated that the peptides PNVA and PNLG form more hydrogen bonds with ACE than their corresponding truncated analogs (NVA and NLG), while the four active peptides bind to the catalytic pocket of ACE mainly through a network of hydrogen bonds.…”

“…These results indicate that the Pro at the N-terminal of the peptides could reform the rigid structure of the peptides, further altering the binding sites between peptides and ACE. These are similar to the observations made by Liu et al [ 35 ], who reported that Leu at the N-terminal of LVKF could alter the binding sites of ACE between LVKF and VKF. In summary, our docking studies suggest that Pro at the N-terminal of peptides can affect both the peptide-binding affinity and orientation of the binding site of ACE.…”

“…Consistent with our experimental studies, the results of molecular docking analysis suggest that the truncation of Pro reduced the binding affinity of PNVA and PNLG as the active peptide PNVA showed the highest binding affinity ( Table 4 ). ACE is a metallo-enzyme with the zinc ion at the active site coordinated by His383, His387 and Glu411 [ 35 ]. As shown in Figure 4 , PNVA forms eleven hydrogen bonds with the residues Asp354, Thr358, Asp393, His331, His491, Tyr501, Gln259, Tyr498 and Lys489 ( Figure 4 A,B).…”

Camel Hemorphins Exhibit a More Potent Angiotensin-I Converting Enzyme Inhibitory Activity than Other Mammalian Hemorphins: An In Silico and In Vitro Study

“…Additionally, the presence of positively charged residues, specifically arginine and lysine, near the C-terminus were also considered to be essential for the ACE inhibitory potential of peptides [56]. Moreover, this phenomenon has already been explained by numerous studies, which indicated that the ACE inhibitory potential of some peptides could be increased by the elongation of N-terminus residues [57][58][59]. Our in silico and in vitro results demonstrate that both camel and non-camel LVV-hemorphin-7 bound more stably to the active site of ACE and produced higher inhibition when compared to shorter hemorphin-7 peptides.…”

Antihypertensive effect of quinoa protein under simulated gastrointestinal digestion and peptide characterization

“…28 Likewise, FP is an ACE inhibitor extracted from cheese whey protein, 29 and some peptides sharing FP as part of their sequences were identified as ACE inhibitory peptides, such as YQKFPQY (IC 50 = 20.08 μM), 30 TFPHGP (IC 50 = 833 μM), 31 LVYPFP (IC 50 = 132 μM), 32 and PLFPK (IC 50 = 41.30 μM). 33 We hypothesized that peptides containing bioactive sequences may exert an inhibition effect against ACE, and the function of hydrolyzate is the result of combined action by many peptides.…”