Prediction of the responsiveness to pharmacological chaperones: lysosomal human alpha-galactosidase, a case of study.

ABSTRACT:

Background

The pharmacological chaperones therapy is a promising approach to cure genetic diseases. It relies on substrate competitors used at sub-inhibitory concentration which can be administered orally, reach difficult tissues and have low cost. Clinical trials are currently carried out for Fabry disease, a lysosomal storage disorder caused by inherited genetic mutations of alpha-galactosidase. Regrettably, not all genotypes respond to these drugs.

Results

We collected the experimental data available in literature on the enzymatic activity of ninety-six missense mutants of lysosomal alpha-galactosidase measured in the presence of pharmacological chaperones. We associated with each mutation seven features derived from the analysis of 3D-structure of the enzyme, two feature

SUBMITTER: Andreotti G 

PROVIDER: S-EPMC3016270 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature