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

Paper ID Volume ID Publish Year Pages File Format Full-Text
34450 45026 2014 7 PDF Available
Title
The inhibitory role of Co2+ on α-glucosidase: Inhibition kinetics and molecular dynamics simulation integration study
Abstract

•The inhibitory effect of Co2+ on alpha-glucosidase: binding mechanisms and the responsive residues of alpha-glucosidase.•Research methods via integrating between inhibition kinetics and computational simulations.•The supportive data from MD simulations for the dynamic action of Co2+ on the inhibition of alpha-glucosidase.•The potent therapeutic action for treating type 2 diabetes mellitus of Co2+.

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.

Keywords
pNPG, p-nitrophenyl α-d-glucopyranoside; pNP, 4-nitrophenol; MES, 2-[N-morpholino]ethanesulfonic acid; ANS, 1-anilino-8-naphthalenesulfonate; MD, molecular dynamicsα-Glucosidase; Co2+; Inhibition kinetics; Unfolding; Molecular dynamics
First Page Preview
The inhibitory role of Co2+ on α-glucosidase: Inhibition kinetics and molecular dynamics simulation integration study
Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 49, Issue 11, November 2014, Pages 1913–1919
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering