Carbohydrate sulfotransferases in glycosaminoglycan biosynthesis

Sulfation is an essential posttranslational modification that involves the covalent attachment of sulfate groups to the hydroxyl or amine group of the acceptor molecule. This modification occurs thanks to a sulfotransferase (ST) activity that requires the presence of a donor group, sulfonucleotide 3′-phosphoadenosine-5′-phosphosulfate. Sulfation is a highly specific reaction modifying glycosaminoglycans (GAGs) at different positions along the polysaccharide chain. However, sulfation follows a specific sulfation code or pattern, ensuring a specific function for each GAG. Therefore, in addition to the composition of GAG polysaccharide, the final sulfation pattern determines the ultimate role of GAGs, thus allowing mediation of the cell–cell and cell-extracellular matrix communication. With the increasing awareness of the importance of the biological role of sulfated GAGs, this chapter will first give a brief overview of the two distinct ST superfamilies and then highlight the sulfation mechanism of GAGs in mammals, mainly discussing the role of the GAG ST isoforms. Finally, the biological roles of sulfated GAGs will be presented along with current biomedical developments.