The inhibitory role of Co2+ on α-glucosidase: Inhibition kinetics and molecular dynamics simulation integration study

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Title
The inhibitory role of Co2+ on α-glucosidase: Inhibition kinetics and molecular dynamics simulation integration study
Author(s)
X Li; Z R Lu; D Shen; Y Zhan; H M Zhou; Q Sheng; Jinhyuk Lee
Bibliographic Citation
Process Biochemistry, vol. 49, no. 11, pp. 1913-1919
Publication Year
2014
Abstract
It is important to study enzyme inhibition of α-glucosidase (EC 3.2.1.20) due to its clinical relevance as a target enzyme for the treatment of type 2 diabetes mellitus. In this study, we investigated Co2+-induced inhibition as well as structural changes of α-glucosidase integrated with computational simulations. α-Glucosidase activity was inhibited by Co2+ in a dose-dependent manner. Co2+ inhibited α-glucosidase in a parabolic non-competitive inhibition reaction (Ki = 0.78 ± 0.08 mM) and directly induced regional unfolding of the enzyme resulting in a slight decrease in hydrophobic surface. The computational simulations using molecular dynamics showed that simulation with Co2+ resulted in a loss of secondary structure by positioning Co2+ near the active site for glucose production, implying that the Co2+ stimulate enzyme unfolding. Our study revealed the mechanism of Co2+ ligand binding mediated structural changes as well as inhibition of α-glucosidase activity, and suggested that Co2+ could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.
Keyword
Co2+Inhibition kineticsMolecular dynamicsaUnfoldingα-Glucosidase
ISSN
0032-9592
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.procbio.2014.08.002
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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