title: Redox regulation of human estrogen sulfotransferase (hSULT1E1).
abstract: Sulfotransferases (SULTs) are enzymes that catalyze the sulfation of hydroxyl-containing compounds. Sulfation regulates hormone activities and detoxifies xenobiotics. Human estrogen sulfotransferase (hSULT1E1) catalyzes the sulfation of estrogens and regulates estrogen bioactivities. Oxidative regulation provides a biological mechanism for regulating enzyme activities in vivo. The oxidative regulation of human SULTs has not been reported. In this study, we used amino acid modification, manipulation of intracellular redox state, and site-directed mutagenesis to study the redox regulation of human SULTs and specifically the mechanism of hSULT1E1 inhibitory regulation by oxidized glutathione (GSSG). Of the four major human SULTs, hSULT1A1, hSULT1A3, and hSULT2A1 do not undergo redox regulation; hSULT1E1, on the other hand, can be redox regulated. GSSG inactivated hSULT1E1 activity in an efficient, time- and concentration-dependant manner. The co-enzyme adenosine 3'-phosphate 5'-phosphosulfate protected hSULT1E1 from GSSG-associated inactivation. A reduced glutathione (GSH) inducer (N-acetyl cysteine) significantly increased while a GSH depletor (buthionine sulfoxamine) significantly decreased hSULT1E1 activity, but both failed to affect the amount of hSULT1E1 protein in human hepatocyte carcinoma Hep G2 cells. Crystal structure suggested that no Cys residues exist near the active sites of hSULT1A1, hSULT1A3, and hSULT2A1, but Cys residues do exist within the active site of hSULT1E1. Site-directed mutagenesis demonstrated that Cys83 is critical for the redox regulation of hSULT1E1. This first report on the redox regulation of human SULTs suggests that the redox regulation of hSULT1E1 may interrupt the regulation and function of estrogens under various physiological and pathological conditions.
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Smarajit
authors.initials: S
authors.lastname: Maiti
authors.forename: Jimei
authors.initials: J
authors.lastname: Zhang
authors.forename: Guangping
authors.initials: G
authors.lastname: Chen
mesh_terms: D019943:Amino Acid Substitution; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015238:Sulfotransferases; C020122:estrone sulfotransferase