Comparative Analysis of Arylsulfatase A and Its Mutants and Pharmacological Chaperone Search

Arylsulfatase A (ASA) is a lysosomal enzyme which catalyzes the desulfurization reaction of cerebroside-3-sulfate. Its mutants, N350S, T391S, W318C and E307K+T391S which were discovered by Önder et. al. in 2009, are linked to Metachromatic Leukodystrophy Disease. These mutants are studied by different computational techniques to pinpoint the regions on the protein that are affected by these local changes. It is predicted that these mutations cause conformational changes on the enzyme leading to inactivity. The mutants which are found to cause instability on the conformation of the enzyme will be investigated to find possible binding sites for candidate pharmacological chaperones. This investigation will be based on computational dockings and molecular dynamics simulations.