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Modeling an Enzyme Active Site using Molecular Visualization Freeware
Published on: December 25, 2021
Effect of Ca(2+) on the activity and structure of α-glucosidase: inhibition kinetics and molecular dynamics
Xin Zhang1, Long Shi2, Xuan Li3
1School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Beijing 100029, PR China.
Abstract:
Understanding the mechanism of inhibition of α-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 α-glucosidase with Ca(2+) and 10-ns molecular dynamics simulations. We found that direct binding of Ca(2+) to the enzyme induced structural changes and inhibited enzyme activity. Ca(2+) inhibited α-glucosidase in a mixed-type reaction (Ki = 27.0 ± 2.0 mM) and directly induced the unfolding of α-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca(2+) ions may interact with α-glucosidase residues and that the Ca(2+) binding sites are associated with the structural changes in α-glucosidase. Our study provides insight into the mechanism of the Ca(2+)-induced structural changes in α-glucosidase and the inhibition of ligand binding. These results suggest that Ca(2+) could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.
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