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LARGE2 generates the same xylose- and glucuronic acid-containing glycan structures as LARGE
Angel Ashikov1, Falk F R Buettner, Birgit Tiemann
1Department of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Glycobiology
|November 9, 2012
Summary
LARGE2 is a bifunctional glycosyltransferase that uses specific sugar donors to create xyloglucuronan. This enzyme performs the same glycosylation reaction as LARGE, which is linked to muscular dystrophy.
Area of Science:
- Biochemistry
- Molecular Biology
- Glycobiology
Background:
- LARGE and LARGE2 are homologous Golgi glycosyltransferases.
- Mutations in LARGE cause muscular dystrophy via dystroglycan underglycosylation.
- The systemic function of LARGE2 remains largely unknown.
Purpose of the Study:
- To elucidate the enzymatic function and substrate specificity of LARGE2.
- To determine if LARGE2 can catalyze the same glycosylation reaction as LARGE.
- To investigate the potential role of LARGE2 in cellular glycosylation processes.
Main Methods:
- Enzymatic assays using UDP-xylose and UDP-glucuronic acid as donor substrates.
- Biochemical characterization of LARGE2 activity.
- Comparison of LARGE2 activity with known LARGE enzyme function.
Main Results:
- LARGE2 functions as a bifunctional glycosyltransferase.
- The enzyme utilizes both UDP-xylose and UDP-glucuronic acid.
- LARGE2 synthesizes a xyloglucuronan composed of alternating xylose and glucuronic acid residues.
- LARGE2 catalyzes the identical glycosylation reaction as LARGE.
Conclusions:
- LARGE2 possesses a distinct enzymatic activity, synthesizing xyloglucuronan.
- The findings reveal a conserved glycosylation mechanism between LARGE and LARGE2.
- This study clarifies the biochemical function of LARGE2, a homolog of the muscular dystrophy-associated LARGE protein.
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