Effect of Ba2+ on the activity and structure of α-glucosidase: inhibition kinetics and molecular dynamics simulation

Abstract

It is important to study enzyme inhibition of α-glucosidase (EC 3.2.1.20) due to its physiological role as well as clinical relevance. In the present study, we examined the effect of Ba2+ on α-glucosidase (EC 3.2.1.20) by integrating enzyme kinetics and computational simulations. The results showed that Ba2+ directly bound to this enzyme and induced inhibition through structural changes. Ba2+ inhibited α-glucosidase in a mixed-type reaction (Ki = 55.50 ± 2.12 mM) and directly induced the regional unfolding of alpha-glucosidase, resulting in a slight hydrophobic exposure. The computational simulations via molecular dynamics showed that Ba2+ directly bound to the active site entrance on α-glucosidase resulting in structural changes in this enzyme. Thus, this study provides insights into the mechanism of Ba2+ ligand binding-induced inhibition and structural change in α-glucosidase to increase the current understanding of the toxicity of Ba2+ on the carbohydrate catabolic enzyme α-glucosidase.