Effect of Ca2+ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulations

Understanding the mechanism of inhibition of alpha-glucosidase (EC 3.2.1.20) is clinically important because of the involvement of this enzyme in type 2 diabetes mellitus. In this study, we conducted inhibition kinetics of alpha-glucosidase with Ca2+ and 10-ns molecular dynamics simulations. We found that direct binding of Ca2+ to the enzyme induced structural changes and inhibited enzyme activity. Ca2+ inhibited alpha-glucosidase in a mixed-type reaction (K-i = 27.0 +/- 2.0 mM) and directly induced the unfolding of alpha-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca2+ ions may interact with alpha-glucosidase residues and that the Ca2+ binding sites are associated with the structural changes in alpha-glucosidase. Our study provides insight into the mechanism of the Ca2+-induced structural changes in alpha-glucosidase and the inhibition of ligand binding. These results suggest that Ca2+ could act as a potent inhibitor of alpha-glucosidase for the treatment of type 2 diabetes mellitus. (C) 2013, The Society for Biotechnology, Japan. All rights reserved.