食品与发酵工业 >

2020 , Vol. 46 >Issue 19: 70 - 77

DOI: https://doi.org/10.13995/j.cnki.11-1802/ts.024327

研究报告

芝麻降压与抗氧化肽QCKH的构效关系、分子拼接及理化性质研究

  • 芦鑫 ,
  • 贾聪 ,
  • 王瑞丹 ,
  • 高锦鸿 ,
  • 张丽霞 ,
  • 孙强 ,
  • 赵谋明 ,
  • 黄纪念
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  • 1(河南省农业科学院 农副产品加工研究中心,河南 郑州,450002);
    2(河南省农产品生物活性物质工程技术研究中心,河南 郑州,450002);
    3(华南理工大学 轻工与食品学院,广东 广州,510640)
第一作者:博士,助理研究员(黄纪念研究员为通讯作者, E-mail:hjinian@sina.com)

收稿日期: 2020-04-28

  修回日期: 2020-06-04

  网络出版日期: 2020-11-02

基金资助

中原科技领军人才项目(194200510014); 河南省科技攻关项目(202102110298); 国家特色油料产业技术体系(CARS-14)

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Study on structure-activity relationship, molecular docking and physicochemical properties of an ACE-inhibitory and antioxidant sesame peptide QCKH

  • LU Xin ,
  • JIA Cong ,
  • WANG Ruidan ,
  • GAO Jinhong ,
  • ZHANG Lixia ,
  • SUN Qiang ,
  • ZHAO Mouming ,
  • HUANG Jinian
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  • 1(Center of Agricultural and Sideline Products Processing of Henan Academy of Agricultural Sciences, Zhengzhou 450002, China);
    2(Henan Engineering Research Centre of Bioactive Substances in Agricultural Products, Zhengzhou 450002, China);
    3(College of Light Industry and Food Science Technology, South China University of Technology, Guangzhou 510640, China)

Received date: 2020-04-28

  Revised date: 2020-06-04

  Online published: 2020-11-02

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摘要

为揭示芝麻7S蛋白源的降血压与抗氧化双活性肽QCKH的构效关系、与血管紧张素转换酶(angiotensin I-converting enzyme,ACE)作用机理、理化特性,采用比较分子相似性指数分析法(comparative molecular similarity indices analysis,CoMSIA)研究构效关系,利用分子拼接揭示QCKH与人体ACE的作用位点,并预测其体内吸收代谢特性,评价外部因素对其活性的影响。结果显示:QCKH的降压性与抗氧化性分别与His4和Cys2有关,氢键与电荷极性是影响活性的主要因素。QCKH通过与ACE的活性口袋S1(Ala354、Tyr523), S2(Gln281、His353、Lys511、His513、Tyr520),活性中心Zn2+及其四面体配位中His387和Glu411发生作用,影响ACE空间结构,引起抑制。ADMET预测QCKH可以经口吸收,不影响体内正常的代谢,安全性高。QCKH在酸性与中性条件下活性稳定,在60 ℃下也能保持稳定,然而对紫外敏感。研究结果为QCKH的结构修饰与应用研究提供了理论参考。

关键词： 芝麻7S球蛋白; 吸收代谢预测; 安全性评价; 稳定性评价; 氨基酸残基

本文引用格式

芦鑫 , 贾聪 , 王瑞丹 , 高锦鸿 , 张丽霞 , 孙强 , 赵谋明 , 黄纪念 . 芝麻降压与抗氧化肽QCKH的构效关系、分子拼接及理化性质研究[J]. 食品与发酵工业, 2020 , 46(19) : 70 -77 . DOI: 10.13995/j.cnki.11-1802/ts.024327

Abstract

In order to reveal the structure-activity relationship, mechanism of interaction with Angiotensin-I converting enzyme (ACE), physicochemical properties of an ACE-inhibitory and antioxidant peptide QCKH derived from sesame 7S globulin, comparative molecular similarity indices analysis (CoMSIA) was employed to explore the structure-activity relationship of QCKH. Then molecular docking was performed to identify the interaction sites of ACE with QCKH. Furthermore, the absorption and metabolism of QCKH were predicted. Finally, the effects of environmental factors on activity of QCKH were evaluated. Results showed the ACE-inhibitory and antioxidation of QCKH were related to His4 and Cys2, respectively. Hydrogen bond and electrostatic flied were dominated factors for ACE-inhibitory and antioxidation. Moreover, QCKH formed bonds with S1 pocket (Ala354, Tyr523), S2 pocket (Gln281, His353, Lys511, His513, Tyr520), active site Zn2+, His387 and Glu411 in its tetrahedral coordination, which changed the spatial structure of ACE and caused inhibition. QCKH was recognized as oral absorption, no interference with normal metabolism in vivo and high safety by ADMET prediction. And the activity of QCKH was stable under acid and neutral conditions, and remained stable below 60 ℃. However, it was sensitive to UV. The above results support the theoretical references for structural modification and application of QCKH.

Key words： sesame 7S globulin; absorption and metabolism of prediction; safety evaluation; stability evaluation; amino acid residue

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