Sulfation

Sulfation or sulfurylation in biochemistry is the enzyme-catalyzed conjugation of a sulfo group (not a sulfate or sulfuryl group) to another molecule.[1] This biotransformation involves a sulfotransferase enzyme catalyzing the transfer of a sulfo group from a donor cosubstrate, usually 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to a substrate molecule's hydroxyl or amine, resulting in a sulfate or sulfamate, respectively. Sulfation is involved in a variety of biological processes, including detoxification, hormone regulation, molecular recognition, cell signaling, and viral entry into cells.[1] It is among the reactions in phase II drug metabolism, frequently effective in rendering a xenobiotic less active from a pharmacological and toxicological standpoint, but sometimes playing a role in the activation of xenobiotics (e.g. aromatic amines, methyl-substituted polycyclic aromatic hydrocarbons). Another example of biological sulfation is in the synthesis of sulfonated glycosaminoglycans, such as heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate. Sulfation is also a possible posttranslational modification of proteins.

For sulfation in lead-acid batteries, see Lead–acid battery § Sulfation and desulfation.
Not to be confused with Sulfonation.

Tyrosine sulfation

Tyrosine sulfation is a posttranslational modification in which a tyrosine residue of a protein is sulfated by a tyrosylprotein sulfotransferase (TPST) typically in the Golgi apparatus. Secreted proteins and extracellular parts of membrane proteins that pass through the Golgi apparatus may be sulfated. Such sulfation was first discovered by Bettelheim in bovine fibrinopeptide B in 1954[2] and later found be present in animals and plants but not in prokaryotes or in yeasts. Sulfation sites are tyrosine residues exposed on the surface of the protein typically surrounded by acidic residues. A detailed description of the characteristics of the sulfation site is available from PROSITE (PROSITE pattern: PS00003). Two types of tyrosylprotein sulfotransferases (TPST-1 and TPST-2) have been identified. Recently identified RaxX protein from most Xanthomonas species contains tyrosine sulfation residue, and mimics the plant peptide hormone PSY (Amano et al., 2007, Pruitt et al., 2015, 2017).

Function

Sulfation plays role in strengthening protein–protein interactions. Types of human proteins known to undergo tyrosine sulfation include adhesion molecules, G-protein-coupled receptors, coagulation factors, serine protease inhibitors, extracellular matrix proteins, and hormones. Tyrosine O-sulfate is a stable molecule and is excreted in urine in animals. No enzymatic mechanism of tyrosine sulfate desulfation is known to exist. By knock-out of TPST genes in mice, it may be observed that tyrosine sulfation has effects on the growth of the mice, such as body weight, fecundity, and postnatal viability.

Regulation

There is very limited evidence that the TPST genes are subject to transcriptional regulation and tyrosine O-sulfate is very stable and cannot be easily degraded by mammalian sulfatases. Tyrosine O-sulfation is an irreversible process in vivo. An antibody called PSG2 shows high sensitivity and specificity for epitopes containing sulfotyrosine independent of the sequence context. New tools are being developed to study TPST's, using synthetic peptides and small molecule screens.[3]

See also

References
  1. Chapman, Eli; Best, Michael D.; Hanson, Sarah R.; Wong, Chi-Huey (2004-07-05). "Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility". Angewandte Chemie International Edition. 43 (27): 3526–3548. doi:10.1002/anie.200300631. ISSN 1521-3773. PMID 15293241.
  2. Bettelheim, F. R. (1954). "Tyrosine-O-sulfate in a peptide from fibrinogen". J. Am. Chem. Soc. 76 (10): 2838–2839. doi:10.1021/ja01639a073.
  3. Byrne, D. P. (2018). "New tools for evaluating protein tyrosine sulfation: tyrosylprotein sulfotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors". Biochemical Journal. 475 (15): 2435–2455. doi:10.1042/BCJ20180266.
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