Yang Cuicui, Xie Tianzhao, Cai Mengmeng, Xu Xiaoting, Li Muzijun, Liu Pengru, Lan Xiongdiao
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Higher Education Institutes Key Laboratory for New Chemical and Biological Transformation Process Technology, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China.
Int J Mol Sci. 2024 Dec 4;25(23):13021. doi: 10.3390/ijms252313021.
Angiotensin-converting enzyme (ACE) inhibitory peptides exhibit antihypertensive effects by inhibiting ACE activity, and the study of the interaction between ACEs and inhibitory peptides is important for exploring new therapeutic strategies. In this study, the ACE-inhibitory peptide isolated from casein hydrolysate with the amino acid sequence Leu-Leu-Tyr (LLY) exhibited high ACE-inhibitory activity and stability, which holds significant implications for biochemistry and pharmaceutical applications. Furthermore, systematic investigations were conducted on the interaction between ACE and LLY through various approaches. The Lineweaver-Burk plot indicated the non-competitive inhibition pattern of LLY, suggesting that it binds to the enzyme at the non-active site, and the results were further validated by a molecular docking study. Additionally, multispectral experiments and atomic force microscopy were conducted to further elucidate the underlying mechanism of peptide activity. The findings indicated that LLY could induce a conformational change in ACE, thereby inhibiting its activity. This study contributes to a deeper understanding of the mechanism of action of ACE-inhibitory peptides and bears important significance for drug development in hypertension.
血管紧张素转换酶（ACE）抑制肽通过抑制ACE活性发挥降压作用，研究ACE与抑制肽之间的相互作用对于探索新的治疗策略具有重要意义。在本研究中，从酪蛋白水解物中分离出的具有Leu-Leu-Tyr（LLY）氨基酸序列的ACE抑制肽表现出高ACE抑制活性和稳定性，这对生物化学和药物应用具有重要意义。此外，通过各种方法对ACE与LLY之间的相互作用进行了系统研究。Lineweaver-Burk图表明LLY为非竞争性抑制模式，表明它在非活性位点与酶结合，分子对接研究进一步验证了该结果。此外，还进行了多光谱实验和原子力显微镜实验以进一步阐明肽活性的潜在机制。研究结果表明，LLY可诱导ACE构象变化，从而抑制其活性。本研究有助于更深入地了解ACE抑制肽的作用机制，对高血压药物开发具有重要意义。
