NDSTs

NDSTs, short for N-deacetylase/N-sulfotransferases, are a family of Golgi-resident enzymes that initiate the N-sulfation step of heparan sulfate biosynthesis. They catalyze two coupled reactions on glucosamine residues within nascent heparan sulfate chains: N-deacetylation of N-acetylglucosamine and subsequent N-sulfation to produce N-sulfated glucosamine. This modification creates substrates for further O-sulfation and for epimerization, shaping the sulfation pattern that governs interactions between heparan sulfate and a wide range of proteins.

There are four NDST isoforms in mammals, NDST1 through NDST4. They share a common domain organization and Golgi localization, with a short cytosolic N-terminus and a catalytic luminal domain. The isoforms exhibit overlapping but distinct tissue expression and activity, with NDST1 generally widely expressed and the others contributing in specific tissues or developmental contexts.

In vivo, NDST activity is critical for the structural diversity of heparan sulfate that modulates signaling pathways such as fibroblast growth factors (FGF), vascular endothelial growth factor (VEGF), Wnt, and Hedgehog, as well as extracellular matrix interactions. Genetic disruption or altered expression of NDSTs can perturb sulfation patterns and affect development, angiogenesis, and cellular responses to growth factors. NDSTs are therefore essential components of the heparan sulfate biosynthetic machinery and are studied to understand how sulfation patterns influence a broad range of biological processes.