Enzyme Function Discovery May Help With Muscular Dystrophy Therapies

Researchers from the University of Iowa have discovered the exact function of the enzyme LARGE, which is critical for normal muscle structure and is involved in several muscular dystrophies. The results, published in Science, may be used to develop large-scale testing of muscular dystrophy therapies.

LARGE adds a critical sugar chain onto the membrane protein dystroglycan, according to a press release. The sugar chain acts like a glue allowing dystroglycan to attach to other proteins and reinforce cell membranes. Without the sugar chain, dystroglycan cannot function properly and can cause muscular dystrophies and brain abnormalities.

“LARGE is a critical enzyme involved in maintaining muscle cell viability,” Kevin Campbell, PhD, professor and head of molecular physiology at the University of Iowa Carver College of Medicine, stated in the release. “It adds on a unique sugar chain that allows the muscle cell to protect its membrane from injury. By figuring out the function of this enzyme, we’ve finally identified this critical sugar link.”

Using nuclear magnetic resonance analysis, the team determined the precise structure of the sugar chain produced by LARGE, which has not been seen before. By understanding the structure and function of the LARGE enzyme, the researchers were able to develop a test to monitor enzyme activity. They also found that boosting LARGE activity in cells from patients with muscular dystrophies was sufficient in restoring dystroglycan function and overcoming defects in the cells.

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