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You are here: The Britz-McKibbin Laboratory > Publications > Functional screening of pharmacological chaperones via restoration of enzyme activity upon denaturation.

Meera Shanmuganathan and Philip Britz-McKibbin (2012)

Functional screening of pharmacological chaperones via restoration of enzyme activity upon denaturation.

Biochemistry, 51(39):7651-3.

Pharmacological chaperones (PCs) are small molecules that stabilize and promote protein folding. Enzyme inhibition is widely used for PC selection; however, it does not accurately reflect chaperone activity. We introduce a functional assay for characterization of PCs based on their capacity to restore enzyme activity that is abolished upon chemical denaturation. Dose-dependent activity curves were performed as a function of urea to assess the chaperone potency of various ligands to beta-glucocerebrosidase as a model system. Restoration of enzyme activity upon denaturation allows direct screening of PCs for treatment of genetic disorders associated with protein deficiency, such as Gaucher disease.

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