Chapter 10: Sulfuryl Transferases and Sulfatases

The most abundant form of sulfur in our oxygenated planet is inorganic sulfate. It can be used for sulfuryl (–SO₃⁻) transfers to cosubstrate nucleophiles once it is metabolically activated as the mixed sulfuric–phosphoric anhydride in adenyl sulfate (AMP–SO₄) or the 3′-phosphorylated adenosine-5′-phosphosulfate (APS) metabolite, designated PAPS. Sulfuryltransfers are often called sulfotransfers although it is the –SO₃⁻ group not SO₄²⁻ being transferred. A range of hydrophobic metabolites are reversibly O- and N-sulfated, while glycosaminoglycans may contain up to approximately 2000 sulfated hexose residues in a single proteoglycan. Protein sulfation occurs predominantly on tyrosine residues, as in the chemokine membrane receptor CCR5 which doubles as HIV receptor when bis-sulfated at the amino terminus. A variety of sulfatases form the complement for removal of sulfuryl groups hydrolytically. The major class of sulfatases have a posttranslational modification converting a cysteine side chain to a formylglycine, introducing an aldehyde functional group to the catalytic inventory. The hydrate form of the aldehyde is thought to be the nucleophile attacking the sulfur in the transferring SO₃⁻ group.