Molecular basis of reduced glucosylceramidase activity in the most common Gaucher disease mutant, N370S.

ABSTRACT: Gaucher disease is caused by the defective activity of the lysosomal hydrolase, glucosylceramidase. Although the x-ray structure of wild type glucosylceramidase has been resolved, little is known about the structural features of any of the >200 mutations. Various treatments for Gaucher disease are available, including enzyme replacement and chaperone therapies. The latter involves binding of competitive inhibitors at the active site to enable correct folding and transport of the mutant enzyme to the lysosome. We now use molecular dynamics, a set of structural analysis tools, and several statistical methods to determine the flexible behavior of the N370S Gaucher mutant at various pH values, with and without binding the chaperone, N-butyl-deoxynojirimycin. We focus on the effect of the chape

SUBMITTER: Offman MN 

PROVIDER: S-EPMC3009936 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature