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

•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.