Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme
Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme
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DOI：
10.1002/jmr.905
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发表时间：
2009-03-01
影响因子：
2.7
通讯作者：
Roque, A. C. A.
中科院分区：
文献类型：
--
作者：
Pina, A. S.;Roque, A. C. A.
高血压或高血压是影响许多个体的病症，并且代表心血管疾病（诸如冠心病和中风）的可控风险因素。一种非药物方法来管理这些包括应用具有抗高血压活性的食物成分。乳蛋白衍生的肽已被开发为天然的消肿剂，即肽Val-Pro-Pro（VPP）和Ile-Pro-Pro（IPP），其已经作为合成药物的潜在替代品在功能性食品中商业化。这些生物活性肽在体外和体内抑制血管紧张素I转化酶（ACE），一种在血压调节中具有重要作用的蛋白质。在这项工作中，我们试图阐明肽和ACE之间的相互作用的可能模式，包括与辅因子Zn 2+结合的机制，并进一步将其与合成药物（Captopril，Enalaprilat和Lisinopril）的已知抑制模式进行对比。生物活性肽Ala-Leu-Pro-Met-His-Ile-Arg（ALPMHIR）也已知抑制酶ACE，但效率低于VPP和IPP，用于对接研究以进行比较。据观察，VPP和IPP获得的最佳对接位姿位于ACE催化位点，与药物相互作用模式非常相似，包括与Zn 2+的配位。对于ALPMHIR，最佳对接位姿位于催化位点外的狭窄ACE通道中，表示与药物建立的相互作用具有更高的亲和能和更少的重复性。版权所有（c）2008约翰威利父子有限公司。
High blood pressure or hypertension is a condition affecting many individuals and represents a controllable risk factor for cardiovascular diseases such as coronary heart disease and stroke. A non-pharmacological approach to manage these includes the application of food components with anti hypertensive activity. Milk protein-derived peptides have been exploited as natural hypotensive agents, namely the peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), already commercialized in functional foods as a potential alternative to synthetic drugs. These bioactive peptides inhibit in vitro and in vivo the Angiotensin I-converting enzyme (ACE), a protein with an important role in blood pressure regulation. In this work, we attempted to elucidate the possible mode of interaction between the peptides and ACE, including mechanisms of binding to the cofactor Zn2+, and further contrast this with the known mode of inhibition exerted by synthetic drugs (Captopril, Enalaprilat and Lisinopril). The bioactive peptide Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR), also known to inhibit the enzyme ACE but with a lower efficiency than VPP and IPP, was utilized in the docking studies for comparison. It was observed that the best docking poses obtained for VPP and IPP were located at the ACE catalytic site with very high resemblance to the drugs mode of interaction, including the coordination with Zn2+. As for ALPMHIR, the best docking poses were located in the narrow ACE channel outside the catalytic site, representing higher affinity energies and fewer resemblances with the interaction established by drugs. Copyright (c) 2008 John Wiley & Sons, Ltd.