High throughput screening for inhibitors of alpha-galactosidase.

ABSTRACT: Fabry disease is a rare X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A (GLA), which catalyzes the hydrolysis of terminal α-galactosyl groups from glycosphingolipids, such as globotriaosylceramide (Gb3). Many of the mutations in the GLA gene are missense alterations that cause misfolding, decreased stability, and/or mistrafficking of this protein. Small molecule compounds that correct the misfolding and mistrafficking, or activate the mutant enzyme, may be useful in the treatment of Fabry disease. We have screened a library of approximately 230,000 compounds using preparations of human recombinant protein and purified coffee bean enzyme in an effort to find activators and inhibitors of this enzyme. Lansoprazole was identified as a small molecule inhibitor of

SUBMITTER: Motabar O 

PROVIDER: S-EPMC3040456 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature