Rational Design of a Highly Specific Prolyl Endopeptidase To Activate the Antihypertensive Effect of Peptides

Mingzhe Ma, Yalong Cong, John Z.H. Zhang, Lujia Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Enzymatic hydrolysis of food-derived proteins to produce bioactive peptides could activate food functions such as antihypertension. However, the diversity of enzymatic hydrolysis products can reduce bioactive peptides’ efficacy. Highly specific proteases can homogenize the hydrolysis products to reduce the production of impotent peptides. In this study, we successfully obtained M. xanthus prolyl endopeptidase mutant Y451M by constraint/free molecular dynamics simulations and binding energy calculations. The specificity of Y451M for proline was increased by 286 % compared to WT, while its activity was almost unchanged. Milk-derived substrates processed with Y451M showed an antihypertensive effect that was 567 % higher than without enzymes. The ability to activate food antihypertension increased 152 % and the use of enzyme by 192 % compared with WT. Specific proteases are thus valuable tools in the processing of complex substrates to obtain bioactive peptides.

Original languageEnglish (US)
Article numbere202200691
JournalChemBioChem
Volume24
Issue number8
DOIs
StatePublished - Apr 17 2023

Keywords

  • antihypertensive agents
  • bioactive peptides
  • enzymatic hydrolysis
  • prolyl endopeptidases
  • specificity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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