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

• Published in: Medicinal chemistry research 2017-02, Vol.26 (2), p.405-413
• Main Authors: Wang, Jie, Chan, Calvin, Huang, Feng-wen, Xie, Jiang-feng, Xu, Hong, Ho, Ka-wai, Zheng, Sheng-gang, Hu, Zhang-li, Lu, Jun, He, Zhen-dan
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Circular dichroism; Dichroism; Enzymatic activity; Enzyme activity; Fluorescence; Hydrogen bonds; Hydrophobicity; Inhibitors; Molecular docking; Original Research; Pepsin; Pharmacology/Toxicology; Spectra
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-016-1760-2

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.