Cellular zwitterionic metabolite analogs simultaneously enhance reaction rate, thermostability, salt tolerance, and substrate specificity of α-glucosidase

• Published in: Bioorganic & medicinal chemistry 2011-05, Vol.19 (10), p.3128-3134
• Main Authors: Deguchi, Eisuke, Koumoto, Kazuya
• Format: Article
• Language: English
• Subjects: alpha-glucosidase; alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Analytical, structural and metabolic biochemistry; betaine; Betaine - chemistry; Betaine - metabolism; Biological and medical sciences; cations; chemical structure; enzyme activity; Enzyme Stability; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Hydrolases; hydrolysis; Ions - chemistry; Ions - metabolism; Kinetics; Metabolite analogs; metabolites; Models, Molecular; Protein Conformation; Saccharomyces cerevisiae - enzymology; Salt tolerance; solutes; Substrate Specificity; Temperature; thermal stability; Zwitterion; zwitterions; α-Glucosidase
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.04.003

We investigated the structural effects of metabolite analogs derived from a naturally-occurring zwitterionic metabolite, glycine betaine, on the activity of several hydrolases. The initial velocities of the hydrolases were enhanced by the addition of the solutes into the buffer solution. Based on a detailed study using α-glucosidases, the acceleration efficiency of the enzymatic activity was strongly induced by solutes possessing bulky and aliphatic ammonium cations, indicating that enhancement of activity by the solutes depended on their chemical structures. Kinetic analysis revealed that the acceleration of the hydrolysis reaction was related to both the decrement of K m and increment of V max values. Furthermore, the addition of the metabolite analogs enhanced not only the rate constant but also the thermostability, salt tolerance, and substrate specificity of α-glucosidase simultaneously through the reduction of conformational perturbation of the enzyme.