Interaction mechanism of a natural medicine product helicid with a typical digestive enzyme trypsin
Interaction mechanism of a natural medicine product helicid with a typical digestive enzyme trypsin
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天然药物产品螺旋肽与典型消化酶胰蛋白酶的相互作用机制
DOI：
10.1080/00387010.2020.1855451
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发表时间：
2020-12
影响因子：
1.7
通讯作者：
Hong Xu
中科院分区：
文献类型：
--
作者：
Min Tang;Limin Wang;Guangyao Zhao;Qingguo Han;Xu Xu;Zheling Zeng;Ming Ying;Zhendan He;Zhangli Hu;Hong Xu
摘要采用多光谱技术和分子模拟方法研究了天然药物豆腐果苷与典型消化酶胰蛋白酶的相互作用机理。荧光猝灭实验表明，豆腐果苷对胰蛋白酶的荧光猝灭是通过动态猝灭和静态猝灭相结合的机制进行的，这是因为豆腐果苷与胰蛋白酶形成了复合物。热力学分析表明，豆腐果苷与胰蛋白酶的结合是熵驱动的，疏水相互作用是稳定复合物的主要力量。应用Förster能量转移理论证明能量转移发生在复合物内。紫外-可见光谱、同步荧光光谱、三维荧光光谱和圆二色光谱表明，豆腐果苷诱导胰蛋白酶构象发生变化，使胰蛋白酶多肽骨架松弛，部分β-折叠和无规卷曲结构转变为α-螺旋结构，且豆腐果苷在复合物中更靠近色氨酸残基而不是酪氨酸残基。分子模拟结果很好地解释了上述实验结果，并进一步暗示，除了疏水相互作用，氢键也有助于稳定豆腐果苷-胰蛋白酶复合物。本研究有助于了解豆腐果苷在人体内的生物化学过程，为天然化合物构效关系的研究以及胰蛋白酶过度活性相关疾病药物的设计和优化提供有用的信息。
Abstract The interaction mechanism of a kind of natural drug helicid with typical digestive enzyme trypsin was investigated using multi-spectroscopic techniques and molecular modeling method. The fluorescence quenching experiments showed that helicid quenched trypsin fluorescence via a combined quenching mechanism of both dynamic and static quenching processes because of the formation of the helicid–trypsin complex. Thermodynamic analyses suggested that the binding of helicid to trypsin was entropy-driven, and that hydrophobic interactions are the main force to stabilize the complex. Förster energy transfer theory applied demonstrated that energy transfer occurred within the complex. Ultraviolet-visible spectroscopy, synchronous fluorescence spectroscopy, three-dimension fluorescence spectroscopy together with circular dichroism spectroscopy indicated that the conformation of trypsin changed induced by helicid with the loosening of the polypeptide backbone of trypsin and its partial β-sheet and random coil structures being transformed into an α-helix structure and that helicid was closer to tryptophan residues than to tyrosine residues within the complex. Molecular simulation results explained the above experimental results very well and further implied that besides hydrophobic interactions, hydrogen bonds also helped stabilize the helicid–trypsin complex. This study is helpful to the understanding of the biochemical process of helicid in the human body and could provide useful information for the studies on the structure–bioactivity relationship of natural compounds, as well as the design and optimization of the drugs for the treatments of trypsin overactivity-related diseases.
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DOI：
10.1002/bio.2704
发表时间：
2015-02
期刊：
Luminescence : the journal of biological and chemical luminescence
影响因子：
--
作者：
Huijun Zuo;L. Tang;Shu Li;Junwei Huang
通讯作者：
Huijun Zuo;L. Tang;Shu Li;Junwei Huang
影响因子：
5.4
作者：
Ha, JH;Lee, DU;Huh, K
通讯作者：
Huh, K
DOI：
10.1016/j.ijbiomac.2016.10.009
发表时间：
2017
影响因子：
8.2
作者：
L. Momeni;B. Shareghi;A. Saboury;S. Farhadian;F. Reisi
通讯作者：
L. Momeni;B. Shareghi;A. Saboury;S. Farhadian;F. Reisi
DOI：
10.1016/j.saa.2015.09.017
发表时间：
2016-01
期刊：
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
影响因子：
--
作者：
Qing Wang;Xiangling Ma;Jiawei He;Qiaomei Sun;Yuanzhi Li;Hui Li
通讯作者：
Qing Wang;Xiangling Ma;Jiawei He;Qiaomei Sun;Yuanzhi Li;Hui Li
影响因子：
13.6
作者：
Yanqing Wang;Chunjian Tan;Shulin Zhuang;P. Zhai;Yun Cui;Qiu-hua Zhou;Hong-Mei Zhang;Z. Fei
通讯作者：
Yanqing Wang;Chunjian Tan;Shulin Zhuang;P. Zhai;Yun Cui;Qiu-hua Zhou;Hong-Mei Zhang;Z. Fei