On the mechanism of aryl sulfotransferase

Abstract

Aryl sulfotransferase IV (EC 2.8.2.1), purified to homogeneity from male rat liver, catalyzes the sulfation of a variety of substituted phenols, including catecholamines, tyrosine esters, and peptides containing NH2-terminal tyrosine residues. An investigation of the mechanism of the enzyme was carried out using 2-chloro-4-nitrophenol as a model substrate. Kinetic, inhibition, and binding studies with aryl sulfotransferase IV are all consistent with a random rapid equilibrium Bi Bi kinetic mechanism with two dead end product inhibitor complexes. Studies of the chemical mechanisms of the enzyme-catalyzed reaction demonstrate that electron-withdrawing substituents decrease the maximal velocity of phenol sulfation. The maximal velocity of the reaction correlates with Hammett sigma p- constants (rho = -0.25). Evidence is presented for the mechanism by which adenosine 3',5'-bisphosphate and aryl sulfotransferase catalyze the transfer of sulfate from 2-chloro-4-nitrophenyl sulfate to other phenols.