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

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Title
Effect of Ca2+ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulations
Author(s)
X Zhang; L Shi; X Li; Q Sheng; L Yao; D Shen; Z R Lu; H M Zhou; Y D Park; Jinhyuk Lee; Q Zhang
Bibliographic Citation
Journal of Bioscience and Bioengineering, vol. 117, no. 6, pp. 696-705
Publication Year
2014
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 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 α-glucosidase in a mixed-type reaction (Ki=27.0±2.0mM) and directly induced the unfolding of α-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca2+ ions may interact with α-glucosidase residues and that the Ca2+ binding sites are associated with the structural changes in α-glucosidase. Our study provides insight into the mechanism of the Ca2+-induced structural changes in α-glucosidase and the inhibition of ligand binding. These results suggest that Ca2+ could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.
Keyword
Inhibition kineticsMolecular dynamicsPNPPNPGSimulationα-GlucosidaseANS
ISSN
1389-1723
Publisher
Soc Bioscience Bioengineering Japan
DOI
http://dx.doi.org/10.1016/j.jbiosc.2013.12.003
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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