Enzyme function could help with muscular dystrophy therapies

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Enzyme function could help with muscular dystrophy therapies

Enzyme Function Could Help With Muscular Dystrophy Therapies


Researchers at the University of Iowa have worked out the exact function of an enzyme that is critical for normal muscle structure and is involved in several muscular dystrophies. The findings, which were published Januarny 6 in the journal Science, could be used to develop rapid, large-scale testing of potential muscular dystrophy therapies.


The enzyme, called LARGE, adds a critical sugar chain onto an important membrane protein called dystroglycan. This sugar chain acts like a glue allowing dystroglycan to attach to other proteins and by doing so, reinforce cell membranes in many tissues including muscle and brain. Dystroglycan does not function properly without this sugar link, and that malfunction causes muscular dystrophies and brain abnormalities.


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The new study shows that the enzyme activity of LARGE has two specific sugar-adding functions -- it transfers the sugars xylose and glucuronic acid. Using nuclear magnetic resonance analysis (NMR), the team was also able to determine the precise structure of the sugar chain produced by LARGE, which has not been seen before.

The study confirmed that this unique sugar chain is responsible for dystroglycan's ability to attach to its protein partners, which include laminin in muscle and neurexin in brain.


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