Clostridium difficile toxins A and B are cation-dependent UDP-glucose hydrolases with differing catalytic activities.

The Journal of Biological Chemistry
W P Ciesla, D A Bobak

Abstract

Toxins A and B of Clostridium difficile are UDP-glucose glucosyltransferases that exert their cellular toxicity primarily through their abilities to monoglucosylate, and thereby inactivate, Rho family small GTPases. Toxin A also hydrolyzes UDP-glucose, although this activity is not well characterized. In this study, we measured the kinetics of UDP-glucose hydrolysis by toxins A and B and found significant differences in the catalytic activities of these two structurally homologous toxins. The toxins displayed similar Michaelis constants (Km) for UDP-glucose, but the maximal velocity (Vmax) of toxin B was approximately 5-fold greater than that of toxin A. Toxins A and B exert their enzymatic actions intracellularly, and, interestingly, we found that each toxin absolutely required K+ for optimal hydrolase activity; Na+ was inactive. The toxins also required certain divalent cations for activity and exhibited a significantly greater Vmax and lower Km in the presence of Mn2+ as compared with Mg2+. We conclude that C. difficile toxins A and B are cation-dependent UDP-glucose hydrolases that differ significantly in their catalytic activities, a finding that may have important implications in understanding their different cytotoxic ef...Continue Reading

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