Enzymes Build Glycan (IMAGE)
Caption
The diagram shows the structure of a critical portion of the glycan that controls the function of the dystroglycan (DG) protein. Without this sugar modification DG does not function properly, and glitches in the construction of the glycan cause the progressive muscle dysfunction and the brain abnormalities that characterize many forms of muscular dystrophy. In a new study published online Aug. 8 in Science, a University of Iowa team has pinpointed not just one, but three enzymes that are required for constructing a key, early section of the glycan. Three enzymes act sequentially to build this section of the DG glycan. The starting point is a mannose sugar (Man) attached to the DG protein. Enzyme 1 in the diagram (called GTDC2) links a glucosamine (GlcN) sugar to this starting mannose. Enzyme 2 (B3GALNT2) then adds a galactosamine sugar (GalN) to the GlcN. Only when this disaccharide is complete can Enzyme 3 -- an unusual type of kinase called SGK196 -- add a phosphate group (P) to the mannose at the beginning of the chain. Earlier work from the UI lab has shown that this phosphate link is required for other enzymes to build the final section of the glycan -- the part that actually allows DG to function.
Credit
University of Iowa
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