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Interaction mechanism of pepsin with a natural inhibitor gastrodin studied by spectroscopic methods and molecular docking

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Abstract

The interaction of gastrodin with pepsin has been investigated by enzyme activity assay, fluorescence, UV–Visible, circular dichroism spectra, and molecular docking. The pepsin activity results suggest that gastrodin is an inhibitor of pepsin. The fluorescence experiments show that gastrodin can quench the fluorescence of pepsin via a static quenching process. The thermodynamic analysis suggests that hydrophobic interaction is the main force between pepsin and gastrodin. UV–Visible and circular dichroism spectra studies suggest that the binding of gastrodin leads to a loosening and unfolding of pepsin backbone with partial α-helix being transformed into β-sheet. All these experimental results have been validated by docking studies, which further show that besides hydrophobic interaction, hydrogen bond also help stabilize the gastrodin–pepsin complex. The results reveal the potential to develop the natural compound gastrodin for the treatment of diseases related to the excessive activity of pepsin.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant 31540012, 31470431, 30570421, 81501213), Guangdong Natural Science Foundation for Major Cultivation Project (2014A030308017), Shenzhen Science and Technology Innovation Committee Grants (JCYJ20150625103526744, JCYJ20120613112512654, JSGG20130411160539208, KQCX20140522111508785, CXZZ20150601110000604, ZDSYS201506031617582), Shenzhen special funds for Bio-industry development (NYSW20140327010012), and Shenzhen Medical Scientific Research Project (201401077).

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    Authors and Affiliations

    1. College of Life Sciences & Oceanography, Shenzhen Key Laboratory of Marine Bioresources and Ecology/Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, China

      Jie Wang, Calvin Chan, Feng-wen Huang, Jiang-feng Xie, Hong Xu, Zhang-li Hu & Jun Lu

    2. School of Femtosecond Education, Shangrao, 334100, China

      Calvin Chan, Ka-wai Ho & Sheng-gang Zheng

    3. Faculty of Health and Environmental Sciences, School of Science, and Institute of Biomedical Technology, Auckland University of Technology, Auckland, 1142, New Zealand

      Jun Lu

    4. School of Medicine, Shenzhen University, Shenzhen, 518060, China

      Zhen-dan He

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    1. Jie Wang
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    2. Calvin Chan
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    3. Feng-wen Huang
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    4. Jiang-feng Xie
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    5. Hong Xu
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    9. Jun Lu
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    Correspondence to Hong Xu or Zhen-dan He.

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    Jie Wang and Calvin Chan contributed equally as co-first authors in this paper.

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    Wang, J., Chan, C., Huang, Fw. et al. Interaction mechanism of pepsin with a natural inhibitor gastrodin studied by spectroscopic methods and molecular docking. Med Chem Res 26, 405–413 (2017). https://doi.org/10.1007/s00044-016-1760-2

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    • DOI: https://doi.org/10.1007/s00044-016-1760-2

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