Glycosaminoglycan sulfotransferase (GAG-ST)

Glycosaminoglycan (GAG) sulfotransferases are a group of Golgi-resident enzymes that play a critical role in the post-translational modification of complex carbohydrates, including heparan sulfate, chondroitin sulfate, and keratan sulfate (Kusche-Gullberg & Kjellén, 2003). By transferring sulfate groups from the universal donor 3-phosphoadenosine 5-phosphosulfate (PAPS) to specific positions on the GAG chain, these enzymes create highly specific binding sites for a variety of signaling molecules, such as growth factors, chemokines, and morphogens (Habuchi et al., 2004). This sulfation code is essential for regulating cell proliferation, migration, and differentiation during development and tissue repair. In various diseases, including cancer and chronic inflammation, the expression of GAG sulfotransferases is often dysregulated, leading to aberrant GAG sulfation patterns that promote tumor angiogenesis, metastasis, and immune evasion (Thelin et al., 2013). Furthermore, specific sulfation patterns are required for the attachment and entry of several human pathogens, including Herpes Simplex Virus and the malaria parasite (Monneau et al., 2016). Consequently, GAG sulfotransferases are emerging as significant therapeutic targets, with research focusing on the development of small-molecule inhibitors and substrate analogs to modulate GAG-protein interactions in oncology and infectious diseases (Karamanos et al., 2018).

Other names

Carbohydrate sulfotransferaseHS-sulfotransferaseCS-sulfotransferaseHeparan sulfate sulfotransferaseChondroitin sulfotransferaseDermatan sulfotransferaseKeratan sulfotransferaseN-deacetylase/N-sulfotransferaseNDSTCHST

Inhibition of the transfer of sulfate groups from the universal donor 3-phosphoadenosine 5-phosphosulfate (PAPS) to glycosaminoglycan chains, thereby modulating the interaction between GAGs and signaling proteins.