Inhibitory effects of daidzein and genistein on trypsin: Insights from spectroscopic and molecular docking studies.
In this work, the inhibitory effect of two isoflavonoids including daidzein and genistein on trypsin and their binding mechanism were determined by spectroscopic and molecular docking approaches. The results indicated that both daidzein and genistein reversibly inhibited trypsin in a competitive manner with IC50 values of 68.01×10(-6)molL(-1) and 64.70×10(-6)molL(-1) and Ki values of 62.12×10(-6)molL(-1) and 59.83×10(-6)molL(-1), respectively. They could spontaneously bind with trypsin mainly through hydrophobic force and electrostatic interactions with a single binding site. Analysis of circular dichrosim spectra and molecular docking revealed that both isoflavonoids bound directly into the catalytic cavity and the microenvironment and secondary structure of trypsin were changed in this process, which caused the inhibition of trypsin activity. All these experimental results and theoretical data in this work would be help in understanding the mechanism of inhibitory effects of daidzein and genistein against trypsin and the potential of isoflavonoid to relieve symptoms of pancreatitis.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Hua-Jin
HJ
Zeng
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Ya-Ping
YP
Wang
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: yangran@zzu.edu.cn.
Ran
R
Yang
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Jing
J
You
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
Ling-Bo
LB
Qu
D055162:Biocatalysis; D020134:Catalytic Domain; D019833:Genistein / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007529:Isoflavones / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry*
D007529:Isoflavones; C004742:daidzein; D019833:Genistein; D014357:Trypsin
Daidzein; Fluorescence spectroscopy; Genistein; Inhibitory activity; Molecular docking; Trypsin