Inhibitory effect of raspberry ketone on α-glucosidase: Docking simulation integrating inhibition kinetics

Int J Biol Macromol. 2018 Jul 1;113:212-218. doi: 10.1016/j.ijbiomac.2018.02.124. Epub 2018 Mar 29.

Abstract

Inhibition of α-glucosidase is directly associated with treatment of type 2 diabetes. In this regard, we conducted enzyme kinetics integrated with computational docking simulation to assess the inhibitory effect of raspberry ketone (RK) on α-glucosidase. RK bound to the active site of α-glucosidase and interacted with several key residues such as ASP68, TYR71, HIS111, PHE157, PHE158, PHE177, GLN181, ASP214, THR215, ASP349, ASP408, and ARG439, as detected by protein-ligand docking simulation. Subsequently, we confirmed the action of RK on α-glucosidase as the non-competitive type of inhibition in a reversible and rapidly binding manner. The relevant kinetic parameters were IC50=6.17±0.46mM and Ki=7.939±0.211mM. Regarding the structure-activity relationship, the higher concentration of RK induced slight modulation of the shape of the active site as monitored by hydrophobic exposure. The tertiary conformational change was linked to RK inhibition, and mostly involved regional changes of the active site. Our study provides insight into the functional role of RK due to its structural property of a hydroxyphenyl ring that interacts with the active site of α-glucosidase. We suggest that similar hydroxyphenyl ring compounds targeting the key residues of the active site might be potential α-glucosidase inhibitors.

Keywords: Inhibition; Raspberry ketone; α-Glucosidase.

MeSH terms

  • Butanones / metabolism*
  • Butanones / pharmacology*
  • Glycoside Hydrolase Inhibitors / metabolism*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Kinetics
  • Molecular Docking Simulation*
  • Protein Conformation
  • Saccharomyces cerevisiae / enzymology
  • alpha-Glucosidases / chemistry
  • alpha-Glucosidases / metabolism*

Substances

  • Butanones
  • Glycoside Hydrolase Inhibitors
  • raspberry ketone
  • alpha-Glucosidases