Osulfotransferases

O-sulfotransferases are enzymes that catalyze the transfer of a sulfate group from the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to hydroxyl groups on acceptor molecules, forming sulfate esters. In glycosaminoglycans, these enzymes create specific sulfation patterns on sugar residues, which modulate the biochemical properties and interactions of the polymers. The reaction typically yields a sulfated product and 3'-phosphoadenosine-5'-phosphate (PAP) as a byproduct.

Most O-sulfotransferases that act on glycosaminoglycans are located in the Golgi apparatus and are Golgi-resident type II transmembrane proteins. Their catalytic domains face the lumen, where they access PAPS and the polysaccharide substrates during biosynthesis. These enzymes exhibit substrate and position specificity, generating diverse sulfation motifs that influence protein binding and signaling.

Key families include the heparan sulfate O-sulfotransferases, such as 2-O-sulfotransferases (HS2ST), 3-O-sulfotransferases (HS3STs), and 6-O-sulfotransferases (HS6STs), which modify heparan sulfate chains at distinct positions. Other enzymes, grouped as carbohydrate sulfotransferases (CHSTs), modify chondroitin sulfate and dermatan sulfate at various O-positions (for example, CHST1-7). The combined activity of these enzymes shapes the sulfation landscape of glycosaminoglycans.

The sulfation pattern generated by O-sulfotransferases influences interactions with growth factors, chemokines, morphogens, and extracellular matrix components, thereby affecting development, cell signaling, and tissue organization. Altered expression or activity of these enzymes can disrupt signaling networks and is associated with developmental disorders, cancer progression, and pathogen interactions. O-sulfotransferases are therefore important for normal physiology and are studied as potential therapeutic targets and biomarkers.