Tyrosine sulfotransferase

Seibert C, Cadene M, Sanhz A, Chait BT, Sakmar TP. Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence. Proc Natl Acad Sci U S A 2002 99(17) 11031— 11036. 

Protein sulfation occurs exclusively at tyrosine residues." It has been suggested that up to 1 % of the tyrosine protein content becomes sulfated, which is the most abundant posttranslational modification for tyrosine, with phosphorylation occurring only on 0.5% of tyrosine protein content." Sulfation occurs mostly on excreted proteins or trans-membrane proteins. Sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST), with PAPS as a cosubstrate (Scheme 4). Like kinases, sulfotransferases have a biological inverse known as sulfatases." ... 

The tyrosine protein sulfotransferase preparations from Golgi-enriched membranes have been used for sulfation of synthetic mono- and multiple-tyrosine peptides related to known sulfation sites in proteins and peptides at analytical levels to establish the enzyme specificities.1f11-13] Preparative sulfations have not been carried out to date. A novel type of arylsulfotransferase produced by Eubacterium A-44 which is part of the human intestinal flora, has recently been discovered.1"1911111 This enzyme catalyzes the transfer of a sulfate group from phenolic sulfate, but not from 3 -phosphadenosine-5 -phosphasulfate, to other phenolic compounds. Using 4-nitrophenylsulfate as a donor substrate and tyrosine-containing peptides and proteins as acceptor substrates it catalyzes the specific sulfation of the tyrosine residues.11111-112 While this enzyme very efficiently sulfates tyrosine derivatives, the... 

The sulfotransferases have been divided into several groups as a result of substrate specificity determinations with purified enzymes and molecular biology studies aryl sulfotransferases are active toward phenols, hydroxylamines, tyrosine esters, and catecholamines alcohol sulfotransferases are active toward primary and secondary steroid alcohols and amine sulfotransferases are active toward arylamines. 

A common mechanism of regulating the state of a protein is via phosphorylation/ dephosphorylation (by kinases and phosphatases, respectively). Serine and threonine residues are the most commonly phosphorylated residues. Tyrosine residues can also be phosphorylated as can histidines. Other mechanisms of controlling the state of proteins include sulfonation and methylation (by sulfotransferases and methyltrans-ferases, respectively). Such posttranslational modifications to the protein are key to the behavior of the target in question and a vHTS study should target the state of interest. One should also be wary of engineered proteins, where one or more residues may have been mutated to alter the biological behavior of said protein. 

With up to 1% of eukaryotic proteins potentially containing sulfotyrosine residues, sulfation of tyrosines is a common posttranslational modification whose biological impact has only just started to be elucidated (Ludeman Stone, 2014 Moore, 2003 Seibert et al., 2008). In humans and most mammals, there are two isoforms of the enzyme responsible for tyrosine sulfation these enzymes are tyrosylprotein sulfotransferase 1 and 2 (TPST-1 and TPST-2) (Moore, 2003 Seibert Sakmar, 2008). TPST-1 and TPST-2 are located in the irans-Golgi network and this limits tyrosine sulfation to secreted or membrane proteins (Moore, 2003 Seibert Sakmar, 2008). Both enzymes utilize the cosubstrate PAPS, or 3Gphosphoadenosine-5 -phosphosulfate, as the sulfate donor to catalyze the sulfation of a tyrosine s phenolic hydroxyl in a substrate protein or peptide as seen in Fig. 1 (Moore, 2003 Seibert Sakmar, 2008). 

Ouyang, Y., Lane, W. S., Moore, K. L. (1998). Tyrosylprotein sulfotransferase Purification and molecular cloning of an enzyme that catalyzes tyrosine O-sulfation, a common posttranslational modification of eukaryotic proteins. Proceedings of the National Academy of Sciences of the United States of America, 95(6), 2896—2901. 

Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases. Biochemistry, 47(43), 11251-11262. 

Teramoto, T., Fujikawa, Y., Kawaguchi, Y., Kurogi, K., Soejima, M., Adachi, R., et al. (2013). Crystal structure of human tyrosylprotein sulfotransferase-2 reveals the mechanism of protein tyrosine sulfation reaction. Nature Communications, 4, 1572. 

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