A new type of sulfation reaction: C-sulfonation for α,β-unsaturated carbonyl groups by a novel sulfotransferase SULT7A1

Abstract

Cytosolic sulfotransferases, SULTs, are cytosolic enzymes that catalyze the transfer of sulfonate to key endogenous compounds, altering the physiological functions of their substrates. SULT enzymes catalyze the O-sulfonation of hydroxy groups or N-sulfonation of amino groups of substrate compounds. Here we report the discovery of C-sulfonation of α, β-unsaturated carbonyl groups mediated by a new SULT enzyme, SULT7A1, and human SULT1C4. Enzymatic assays revealed that SULT7A1 is capable of transferring the sulfonate group from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to the α-carbon of α, β-unsaturated carbonyl-containing compounds, including cyclopentenone prostaglandins as representative endogenous substrates. Structural analyses of SULT7A1 suggest that the C-sulfonation reaction is catalyzed by a novel mechanism mediated by His and Cys residues in the active site. Ligand-activity assays demonstrated that sulfonated 15-deoxy prostaglandin J2 exhibits antagonist activity against the prostaglandin receptor EP2 and the prostacyclin receptor IP. Modification of α, β-unsaturated carbonyl groups via the new prostaglandin-sulfonating enzyme, SULT7A1, may regulate the physiological function of prostaglandins in the gut. Discovery of C-sulfonation of α, β-unsaturated carbonyl groups will broaden the spectrum of potential substrates and physiological functions of SULTs.