Preliminary crystallographic studies on the human tyrosylprotein sulfotransferase-2 and peptide complex

Abstract

Post-translational modifications, such as tyrosine sulfation, affect protein function and cellular communication. Tyrosine sulfation is important in a variety of biological processes such as the regulation of immune responses and pathogen interactions and it is mediated by tyrosylprotein sulfotransferase (TPST). TPST catalyzes tyrosine O-sulfate synthesis by transferring the sulfonate group of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the hydroxyl group of the tyrosine residue of the target protein. TPST is a membrane glycoprotein with a type II transmembrane topology and is located in the trans-Golgi network. In previous studies, crystal structure of TPST1 and TPST2 provided overall structural insights and revealed the specific residues that interact with their substrates. In this study, I provided the molecular basis of TPST2 underlying mechanism for substrate specificity for the interaction with peptides using X-ray crystallography and ligand docking methods. These results could be helpful for the new drug development that exploit the specific interactions of TPST2 with its inhibitors to modulate the activity of TPST2 in disease.