During the biosynthesis of heparan sulphate (HS) in the Golgi compartment, the first modification enzyme, glucosaminyl N-deacetylase/N-sulphotransferase (NDST), starts to work on the growing HS polysaccharide chain. This enzyme defines the overall design of the sulphation pattern, which will determine the ability of the HS chain to interact with target molecules. NDST removes acetyl groups from glucosamine residues and replaces them with sulphate groups. These N-sulphate groups are essential for further modification during biosynthesis; without N-sulphation, no O-sulphation or conversion of glucuronic acid into iduronic acid will occur. Four NDST isoforms, transcribed from four genes, have been identified. Much of our work is concentrated on how the enzymes are organized within the Golgi compartment and the identification of interacting partners. In addition, we study mice in which the gene encoding NDST-1 or NDST-2 has been knocked out. NDST-1 knockout mice with altered HS structure die at birth due to lung failure, whereas lack of NDST-2 results in abnormal mast cells. Since NDSTs have a key role in HS design (see above), these mice can be used to study HS function. Areas of interest are cell differentiation, growth, inflammation, cancer, lipid metabolism and microbial infection.
Conference Article| April 01 2003
Glucosaminyl N-deacetylase/N-sulphotransferases in heparan sulphate biosynthesis and biology
Biochem Soc Trans (2003) 31 (2): 340-342.
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L. Kjellén; Glucosaminyl N-deacetylase/N-sulphotransferases in heparan sulphate biosynthesis and biology. Biochem Soc Trans 1 April 2003; 31 (2): 340–342. doi: https://doi.org/10.1042/bst0310340
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