Sulfotransferase 1A1 Substrate Selectivity: A Molecular Clamp Mechanism.

ABSTRACT: The human cytosolic sulfotransferases (SULTs) regulate hundreds, perhaps thousands, of small molecule metabolites and xenobiotics via transfer of a sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and primary amines of the recipients. In liver, where it is abundant, SULT1A1 engages in modifying metabolites and neutralizing toxins. The specificity of 1A1 is the broadest of any SULT, and understanding its selectivity is fundamental to understanding its biology. Here, for the first time, we show that SULT1A1 substrates separate naturally into two classes: those whose affinities are either enhanced ∼20-fold (positive synergy) or unaffected (neutral synergy) by the presence of a saturating nucleotide. kcat for the positive-synergy substrates is shown to

SUBMITTER: Cook I 

PROVIDER: S-EPMC4870834 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature