The Activity And Structure Effection Of Co²⁺ And Ba²⁺ On α-glucosidase

Alpha-glucosidase (EC3.2.1.20) is a target enzyme to treat type2diabetes mellitus, hence,due to the clinical relevance, it is important to study this enzyme’s inhibition. In this study, weinvestigated Co2+-induced inhibition as well as structural changes of α-glucosidase integratingwith computational simulations. The activity of α-glucosidase was inhibited by Co2+in adose-dependent manner. Co2+inhibited α-glucosidase in a parabolic non-competitive inhibitionreaction (Ki=0.78±0.08mM) and directly induced the regional unfolding of the enzymeresulting in a slight decrease of hydrophobic surface. The computational simulations usingmolecular dynamics showed that the simulation with Co2+ions lost the secondary structure bypositioning Co2+ions near the active site for glucose degradation, implying that the Co2+ions canstimulate the unfolding of the enzyme. Our study revealed the mechanism of Co2+ligand bindingmediated structural change as well as inhibition of α-glucosidase, and suggested that Co2+couldact as a potent inhibitor of α-glucosidase for the treatment of type2diabetes mellitus.In the present study we also explored the effect of Ba2+on α-glucosidase with integratingenzyme kinetics and computational simulations. We found that Ba2+directly bound to theenzyme and induced inhibition accompanying the structural changes. Ba2+inhibitedα-glucosidase in a mixed-type reaction (Ki=55.50±2.12mM) and directly induced the regionalunfolding of α-glucosidase, resulting in a slight hydrophobic exposure. The computationalsimulations via conducting molecular dynamics showed that Ba2+ions could directly bind theentrance of active site on α-glucosidase and influence the structural change. The structuralchanges might cause the loss of activity induced by Ba2+proved by the experiments. Our studyprovides insights into the mechanism of Ba2+ligand binding induced inhibition and structuralchange of α-glucosidase, and to understand the toxicity of Ba2+with the respect of how to act onthe carbohydrate catabolic enzyme.