Engineering sulfotransferases to modify heparan sulfate

Distinctive expression patterns of heparan sulfate O-sulfotransferases and regional differences in heparan sulfate structure in chick limb buds.

The skeletal tissue development and patterning in chick limb buds are known to be under the spacio-temporal control of various heparin-binding cell growth factors such as fibroblast growth factors and bone morphogenetic proteins. Different structural regions on heparan sulfate (HS) chains of proteoglycans could be implicated in regional differences in the binding capacities of these cell growth...

Functional analysis of conserved cysteines in heparan sulfate N-deacetylase-N-sulfotransferases.

N-Deacetylase-N-sulfotransferases (NDANST) catalyze the two initial modifications of the polysaccharide precursor in the biosynthesis of heparin and heparan sulfate. These modifications are the gating steps in establishing growth factor protein-binding domains of these glycosaminoglycans. We have undertaken a structure-activity analysis of the 841-amino acid Golgi-luminal portion of the rat liv...

In Vitro Studies of the Substrate Specificities of Heparan Sulfate 2-O- and 6-O-sulfotransferases

Biological functions of N-deacetylase/N-sulfotransferases in the biosynthesis of heparan sulfate/heparin

Heparan sulfate/heparin (HS/HP) is a large complex carbohydrate and binds various proteins, such as FGF, TGFβ/Dpp, Wnt/Wingless, Hedgehog and anti-thrombin III. In the biosynthesis of HS/HP, N-deacetylation and N-sulfation of N-acetyl glucosamine are catalyzed by a single polypeptide, NDST, and have important roles in forming unique sequences for binding those proteins. Four NDST isozymes are f...

Heparan Sulfate Biosynthesis

Heparan sulfate is perhaps the most complex polysaccharide known from animals. The basic repeating disaccharide is extensively modified by sulfation and uronic acid epimerization. Despite this, the fine structure of heparan sulfate is remarkably consistent with a particular cell type. This suggests that the synthesis of heparan sulfate is tightly controlled. Although genomics has identified the...