MOLECULAR SPECIFICITY OF ARYL SULFOTRANSFERASE-IV (TYROSINE-ESTER SULFOTRANSFERASE) FOR XENOBIOTIC SUBSTRATES AND INHIBITORS

Studies on the interactions of benzylic alcohols, aldehydes, and carbo xylic acids with homogeneous preparations of aryl sulfotransferase (AS T) IV have yielded information about the nature of the active site of the enzyme. Lipophilicity and stereochemical configuration of benzylic alcohols are key factors in determining their interaction with the ac tive site of AST IV, Furthermore, aldehydes and carboxylic acids corre sponding to the subsequent oxidation states derived from benzylic alco hols are inhibitors of the enzyme. Additional investigations on the ca talytic specificity of AST IV indicate that both primary and secondary N-hydroxy arylamines can serve as substrates for the enzyme. These re sults with benzylic alcohols, aldehydes, carboxylic acids, and N-hydro xy arylamines have yielded insight into some of the parameters importa nt in recognition of substrates and inhibitors by the active site of t he enzyme and should be useful both in understanding in vivo metabolic interactions and in designing appropriate new inhibitors to use as se lective probes for the role of sulfation in metabolism of specific xen obiotics.