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Predicting Successful Chaperoning Of Fabry Disease Mutants Via Computation, Priyank Patel

Masters Theses

Fabry disease is an inherited X-linked recessive disorder caused by mutations in the galactosidase alpha (GLA) gene, leading to deficiencies in α-galactosidase A (α-GAL) enzyme production. α-GAL, a lysosomal glycosidase, catalyzes the removal of a terminal α-galactose; however, loss of α-GAL activity leads to accumulation of globotriaosylceramide (an endogenous substrate) and the eventual onset of the disease. Approved treatments for Fabry disease include enzyme replacement therapy and pharmacological chaperone therapy. In the latter treatment, 1-deoxygalactonojirimycin (DGJ), a pharmacological chaperone, is administered to Fabry disease patients, leading to increased enzymatic activity. The DGJ iminosugar acts as a competitive inhibitor …