کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
20640 | 43184 | 2014 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Effect of Ca2+ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulations Effect of Ca2+ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulations](/preview/png/20640.png)
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 ± 2.0 mM) 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.
Journal: Journal of Bioscience and Bioengineering - Volume 117, Issue 6, June 2014, Pages 696–705