title: Paradigms of sulfotransferase catalysis: the mechanism of SULT2A1.
abstract: Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of signaling small molecules via transfer of the sulfuryl moiety (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyls and primary amines of acceptors. Sulfonation controls the affinities of ligands for their targets, and thereby regulates numerous receptors, which, in turn, regulate complex cellular responses. Despite their biological and medical relevance, basic SULT mechanism issues remain unresolved. To settle these issues, and to create an in-depth model of SULT catalysis, the complete kinetic mechanism of a representative member of the human SULT family, SULT2A1, was determined. The mechanism is composed of eight enzyme forms that interconvert via 22 rate constants, each of which was determined independently. The result is a complete quantitative description of the mechanism that accurately predicts complex enzymatic behavior. This is the first description of a SULT mechanism at this resolution, and it reveals numerous principles of SULT catalysis and resolves previously ambiguous issues. The structures and catalytic behaviors SULTs are highly conserved; hence, the mechanism presented here should prove paradigmatic for the family.
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461-1926.
authors: Ting
authors: T
authors: Wang
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461-1926.
authors: Ian
authors: I
authors: Cook
authors: Departments of Pharmacology and Toxicology, University of Alabama School of Medicine at Birmingham, Birmingham, Alabama 35294-0019 and.
authors: Charles N
authors: CN
authors: Falany
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461-1926. Electronic address: tom.leyh@einstein.yu.edu.
authors: Thomas S
authors: TS
authors: Leyh
mesh_terms: D055162:Biocatalysis; D003687:Dehydroepiandrosterone / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D010724:Phosphoadenosine Phosphosulfate / Q000737:chemistry; D011485:Protein Binding; D015238:Sulfotransferases / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D003687:Dehydroepiandrosterone; D010724:Phosphoadenosine Phosphosulfate; D015238:Sulfotransferases; C028152:alcohol sulfotransferase
keywords: DHEA; Enzyme Mechanism; Ligand-binding protein; Metabolic Regulation; Metabolism; Pre-steady State; Rate Constant; SULT2A1; Substrate Inhibition; Sulfotransferase