Tyrosine sulfation as a protein post-translational modification.

Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions.

Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism.

INTRODUCTION: Cytosolic sulfotransferases (SULTs), one of the vital enzymes of detoxication, catalyze the sulfation of native and exogenous hydrophobic molecules. Xenobiotic accumulation can induce a variety of diseases, including cancers. Sulfation facilitates the solubilization and removal of xenobiotics. However, sulfation may activate the pharmacological activities of xenobiotics. AREAS COVERED: The purpose of this review was to correlate the sequence, structure and function of SULTs. We focused on understanding the sulfation mechanisms of SULT through its sequence variation. We selectively reviewed SULT drug substrates, explained the enzyme-catalyzed sulfation reaction and its kinetic mechanisms, and the effect of amino acid sequence variation, such as single-nucleotide polymorphism, on the enzyme function. EXPERT OPINION: A wealth of information is available in the literature for understanding the detailed mechanisms underlying xenobiotic sulfation. We reviewed information regarding the sequence, structure and reaction mechanism of SULTs and explained how SULT activities altered. In addition to revealing the SULT kinetics, the mRNA expression of specific SULTs in tissues that revealed their distribution in tissues also affects overall SULT activities. Understanding of the structure-function relationship and the reaction mechanism of SULTs is valuable for understanding, preventing and treating diseases.