It is important to study enzyme inhibition of alpha-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 alpha-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 alpha-glucosidase in a mixed-type reaction (K-i = 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 alpha-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 alpha-glucosidase to increase the current understanding of the toxicity of Ba2+ on the carbohydrate catabolic enzyme alpha-glucosidase. (C) 2015 Elsevier Ltd. All rights reserved.