Mechanistic study on the facilitation of enzymatic hydrolysis by α-glucosidase in the presence of betaine-type metabolite analogs

Recently we reported that betaine-type metabolite analogs structure-dependently facilitate enzymatic hydrolysis reaction for α-glucosidases, β-glucosidases, and alkaliphosphatases. To understand the facilitation mechanism for enzymes, in this study we expanded the analog library and measured the properties of analog solutions. The structural investigation on α-glucosidase-mediated hydrolysis reaction indicated that suitable structures to facilitate the enzyme reaction efficiently should have the ammonium cation in the betaine structure possess triplicate aliphatic chains from C1 to C7 without any polar functional groups. Analyses of the solution properties revealed that such analogs possess a large hydration layer with low water density. Such a specific hydration environment is generated by the characteristic structure of the betaine-type metabolite analogs. The characteristic hydration indirectly regulates enzyme activity and stability. These findings not only increase our understanding enzyme activation by betaine-type metabolite analogs, but also will contribute to the molecular design of enzyme regulators.

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