Mechanistic studies of beta-arylsulfotransferase IV.
Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various molecules including small-molecule drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-molecule inhibitors. A linear free-energy analysis in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by beta-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Brønsted coefficients (beta(nuc) and beta(lg)) are +0.33 and -0.45, giving Leffler alpha values of 0.19 and 0.61 for the forward and reverse reactions, respectively.
Chapman
Eli
E
Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bryan
Marian C
MC
Wong
Chi-Huey
CH
D000595:Amino Acid Sequence; D015239:Arylsulfotransferase / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D003600:Cytosol / Q000201:enzymology; D005461:Fluorine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010100:Oxygen / Q000737:chemistry; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
D005461:Fluorine; D015239:Arylsulfotransferase; D010100:Oxygen