Characterization of heparan sulfate N-deacetylase/N-sulfotransferase isoform 4 using synthetic oligosaccharide substrates

• Published in: Biochimica et biophysica acta Vol. 1862; no. 3; pp. 547 - 556
• Main Authors: Li, Yi-Jun, Yin, Feng-Xin, Zhang, Xin-Ke, Yu, Jie, Zheng, Shuang, Song, Xin-Lei, Wang, Feng-Shan, Sheng, Ju-Zheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2018
• Subjects: biochemical pathways; Biosynthesis; Catalytic mode; enzyme activity; Heparan sulfate; humans; N-deacetylase/N-sulfotransferase; oligosaccharides; Regulatory mechanism; substrate specificity; Heparan sulfate; Biosynthesis; N-deacetylase/N-sulfotransferase; Catalytic mode; Regulatory mechanism
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2017.11.016

The final structure of heparan sulfate chains is strictly regulated in vivo, though the biosynthesis is not guided by a template process. N-deacetylase/N-sulfotransferase (NDST) is the first modification enzyme in the HS biosynthetic pathway. The N-sulfo groups introduced by NDST are reportedly involved in determination of the susceptibility to subsequent processes catalyzed by C5-epimerse and 3-O-sulfotransferases. Understanding the substrate specificities of the four human NDST isoforms has become central to uncovering the regulatory mechanism of HS biosynthesis. Highly-purified recombinant NDST-4 (rNDST-4) and a selective library of structurally-defined oligosaccharides were employed to determine the substrate specificity of rNDST-4. Full-length rNDST-4 lacks obvious N-deacetylase activity, and displays only N-sulfotransferase activity. Unlike NDST-1, NDST-4 did not show directional N-sulfotransferase activity while the N-deacetylase domain was inactive. Individual NDST-4 could not effectively assume the key role in the distribution of N-S domains and N-Ac domains in HS biosynthesis in vivo. •Full-length NDST-4 lacks N-deacetylase activity.•NDST-4 displays only N-sulfotransferase activity.•N-sulfotransferase activity of NDST-4 did not show directional characteristic.•NDST-4 plays limited role in heparan sulfate biosynthesis.