School of Food Science and Technology, Dalian Polytechnic University, Dalian, P.R. China.
National Engineering Research Center of Seafood, Dalian, P.R. China.
J Food Biochem. 2021 Jul;45(7):e13779. doi: 10.1111/jfbc.13779. Epub 2021 Jun 1.
In this article, the selective inhibition of several tyrosine-containing dipeptides on N and C domain of ACE (angiotensin-converting enzyme) was studied, and the interaction mode of ACE and inhibitors was simulated by molecular docking. MTT assay was used to detect the effect of dipeptide on human umbilical vein endothelial cells (HUVEC). The results showed that the food-derived dipeptides AY (Ala-Tyr), LY (Leu-Tyr), and IY (Ile-Tyr) containing tyrosine at the C-terminal were favorable structures for selective inhibition of ACE C-domain. These dipeptides showed competitive and mixed inhibition patterns, while the dipeptides EY (Glu-Tyr), RY (Arg-Tyr), FY (Phe-Tyr), and SY (Ser-Tyr) showed noncompetitive inhibition. Food-derived dipeptides containing tyrosine have no cytotoxicity on HUVEC cells, which provides a basis for the application of food-derived tyrosine dipeptides as antihypertensive peptides. This study provides a theoretical basis for exploring the selective inhibition mechanism of ACE inhibitory peptides containing tyrosine residue. PRACTICAL APPLICATIONS: Angiotensin-converting enzyme (ACE) is a two-domain dipeptidyl carboxypeptidase, which is a key enzyme to regulate blood pressure. ACE has two active sites, C- and N-domain, which have high catalytic activity. Although the amino acid sequences of the two active sites have 60% similarity, there are some differences in structure and function. The action mechanism of ACE domain should be clarified, and the structure-activity relationship between inhibitors and ACE domain has not been systematically studied. The aim of this study was to identify the selective inhibitory effect of food-derived tyrosine dipeptides on the domain of ACE. This provides a new idea for finding new antihypertensive drugs with less side effects.
在本文中，研究了几种含酪氨酸二肽对 ACE（血管紧张素转换酶）的 N 和 C 结构域的选择性抑制作用，并通过分子对接模拟了 ACE 与抑制剂的相互作用模式。MTT 法检测二肽对人脐静脉内皮细胞（HUVEC）的作用。结果表明，C 末端含有酪氨酸的食源性二肽 AY（Ala-Tyr）、LY（Leu-Tyr）和 IY（Ile-Tyr）是 ACE C 结构域选择性抑制的有利结构。这些二肽表现出竞争性和混合抑制模式，而二肽 EY（Glu-Tyr）、RY（Arg-Tyr）、FY（Phe-Tyr）和 SY（Ser-Tyr）表现出非竞争性抑制。含酪氨酸的食源性二肽对 HUVEC 细胞无细胞毒性，为食源性酪氨酸二肽作为降压肽的应用提供了依据。本研究为探讨含酪氨酸残基的 ACE 抑制肽的选择性抑制机制提供了理论依据。实际应用：血管紧张素转换酶（ACE）是一种二结构域二肽羧基肽酶，是调节血压的关键酶。ACE 有两个活性位点，C 位和 N 位，具有很高的催化活性。虽然两个活性位点的氨基酸序列有 60%的相似性，但在结构和功能上还是存在一些差异。应阐明 ACE 结构域的作用机制，系统研究抑制剂与 ACE 结构域的构效关系。本研究旨在确定食源性酪氨酸二肽对 ACE 结构域的选择性抑制作用。这为寻找副作用更小的新型降压药物提供了新的思路。
