Sandbox GGC14: Difference between revisions

Defects in human a-Galactosidase gene can cause Fabry disease, a lysosomal storage disorder characterized by the buildup of a-galactosylated substrates in the tissues.  It is an X-linked inherited disorder that affects 1 in 40,000 males.  It is often characterized by chronic pain, vascular degeneration, cardiac abnormalities, as well as other symptoms.  The disease can show different levels of severity correlated with the amount of residual enzymatic activity.  Organs affected can include the eyes, liver, kidney, and heart.  More severe forms generally results from a complete loss of enzymatic activity, while milder phenotypes typically show some enzyme activity.  Most people suffering from Fabry disease have a single point mutation in the gene, and over 400 missense and nonsense mutations have been identified.  Other lysosomal storage disorder include the inherited diseases Tay-Sachs, Sandhoff, and Gaucher diseases.

The structure of the enzyme contains <scene name='78/781216/1t0o_alpha-galactosidase/8'>4 N-linked oligosaccharides</scene> comprised of 17 monosaccharides (15 monosaccharides while complexed with galactose).  It also contains 2 domains, an <scene name='78/781216/1t0o_alpha-galactosidase/9'>N-terminal domain</scene> comprised of many a/B barrels, as well as a <scene name='78/781216/1t0o_alpha-galactosidase/10'>C-terminal domain</scene> that has an anti-parallel B-structure.