PDF(Pubmed)
Abstract：
Cytosolic sulfotransferases (SULTs) are cytosolic enzymes that catalyze the transfer of sulfonate group 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. In this study, 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 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.
摘要：
胞质磺基转移酶（SULTs）是催化磺酸盐基团转移到关键内源性化合物的胞质酶，改变其底物的生理功能。SULT酶催化底物化合物的羟基的O-磺化或氨基的N-磺化。在这项研究中,我们报道了α的C-磺化的发现，一种新的SULT酶介导的β-不饱和羰基,SULT7A1和人SULT1C4。酶分析显示，SULT7A1能够将磺酸盐基团从3'-磷酸腺苷5'-磷酸硫酸盐转移到α的α碳，含β-不饱和羰基化合物,包括环戊烯酮前列腺素作为代表性内源性底物。SULT7A1的结构分析表明，C-磺化反应是由活性位点中的His和Cys残基介导的新机制催化的。配体活性测定表明，磺化的15-脱氧前列腺素J2对前列腺素受体EP2和前列环素受体IP具有拮抗剂活性。α的修饰,β-不饱和羰基通过新的前列腺素磺化酶，SULT7A1可以调节肠道中前列腺素的生理功能。α的C-磺化的发现，β-不饱和羰基基团将拓宽潜在底物的光谱和SULTs的生理功能。
