a-NAGAL, and a-NAGALEL enzymes for research purposes. All enzymes could be
visualized with activity-based probes covalently binding in their catalytic pocket.
Characterization of purified proteins indicated that a-NAGALEL is improved in activity toward artificial 4MU-a-galactopyranoside. Recombinant a-NAGALEL and a-NAGAL are not neutralized by Ab-positive FD serum tested and are more stable in human plasma than a-GAL. Both enzymes hydrolyze the lipid substrates Gb3 and Lyso-Gb3 accumulating in Fabry patients. The addition to FD sera of a-NAGALEL, and to a lesser extent that of a-NAGAL, results in a reduction of the toxic Lyso-Gb3. In conclusion, our study suggests that modified a-NAGALEL might reduce excessive Lyso-Gb3 in FD serum. This neo-enzyme can be produced in Nicotiana benthamiana and might be further developed for the treatment of FD aiming at reduction of circulating Lyso-Gb3.