Carbohydrate sulfotransferase

Carbohydrates are suitable for such a wide variety of functions due to the diversity in structure generated from monosaccharide composition, glycosidic linkage positions, chain branching, and covalent modification.

[4] As extracellular compounds, sulfated carbohydrates are mediators of intercellular communication, cellular adhesion, and ECM maintenance.

While cytosolic sulfotransferases play a metabolic role by modifying small molecule substrates such as steroids, flavonoids, neurotransmitters, and phenols, carbohydrate sulfotransferases have a fundamental role in extracellular signalling and adhesion by generating unique ligands through the modification of carbohydrate scaffolds.

[14][15] Heparan sulfate is a glycosaminoglycan (GAG) that is linked by xylose to serine residues of proteins such as perlecan, syndecan, or glypican.

[17] Heparan sulfates are also known to interact with growth factors, cytokines, chemokines, lipid and membrane binding proteins, and adhesion molecules.

[18] Carbohydrate sulfotransferases are of great interest as drug targets because of their essential roles in cell-cell signalling, adhesion, and ECM maintenance.

Their roles in blood coagulation, chronic inflammation, and cornea maintenance mentioned in the Biological Function section above are all of interest for potential therapeutic purposes.

[19] In contrast, heparan sulfate complexes have been shown to bind to HIV-1 and prevent it from entering the cell through its intended target, the CD4 receptor.

Figure 1: A general carbohydrate sulfotransferase reaction. PAPS is shown as the activated sulfate donor; PAPS is the sulfate donor in eukaryotic cells.
Figure 2: The mechanism by which carbohydrate sulfotransferase catalyzes the transfer of a sulfonyl group to a carbohydrate group in a glycoprotein or glycolipid is analogous to the mechanism by which a kinase catalyzes a phosphoryl group. Both enzymes use a lysine residue in their active sites to coordinate to their cosubstrates; the ATP cosubstrate in the kinase mechanism is analogous to the PAPS in the carbohydrate sulfotransferase mechanism (green). Red shows the group being transferred; note that the transfer is coordinated around the lysine. Black is the substrate. Sia stands for sialic acid. [ 6 ] [ 9 ]
Figure 3: Transition state for catalyzed sulfation as proposed by Chapman et al. 2004. [ 12 ] Note the use of the conserved lysine and histidine residues.