Mechanism of Inhibition of Jack Bean α-Mannosidase by Swainsonine

The indolizidine alkaloid, swainsonine, was previously shown to be a potent inhibitor of lysosomal and jack bean alpha-mannosidase (Dorling, Huxtable, Colegate 1980 Biochem J 191: 649-651). We examined the effects of various concentrations of this alkaloid on a number of commercially available glycosidases and found swainsonine to be quite specific for alpha-mannosidase (50% inhibition at 1-5 x 10(-7) molar). Optimum inhibition was observed after a 2-minute preincubation of enzyme and inhibitor. Lineweaver-Burk plots of substrate concentration versus velocity in the presence of various amounts of swainsonine showed considerable curvature at high substrate concentrations, suggesting that swainsonine may be a competitive inhibitor that binds tightly to the enzyme and is only slowly removed. Periodate oxidation of swainsonine completely destroyed its inhibitory activity.