Sulfation

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Sulfation in biochemistry is the enzyme-catalyzed addition of sulfate to another molecule. It often refers to a phase II enzyme reaction. This biotransformation process uses its cosubstrate 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to transfer sulfate to a xenobiotic. Most of the time this is effective in rendering the xenobiotic less active from a pharmacological and toxicological standpoint, but sometimes it plays a role in the activation of xenobiotics (e.g. aromatic amines, methyl substituted polycyclic aromatic hydrocarbons).

Another example of a biological sulfation reaction is in the creation of sulfated glycosaminoglycans. Here, the sulfate group is being added either via oxygen (O-sulfation) or nitrogen (N-sulfation).

Tyrosine sulfation[edit]

Sulfation is also a possible posttranslational modification of protein. The target amino acid is tyrosine and the reaction is called tyrosine sulfation.

Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. Secreted proteins and extracellular parts of membrane proteins that pass through the Golgi apparatus may be sulfated. Sulfation was first discovered by Bettelheim in bovine fibrinopeptide B in 1954[1] and later found be present in animals and plants but not in prokaryotes or in yeast.

Function[edit]

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.

Mechanism[edit]

Sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST) in Golgi apparatus. The reaction catalyzed by TPST is a transfer of sulfate from the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the side-chain hydroxyl group of a tyrosine residue. 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)[1]. Two types of tyrosylprotein sulftotransferases (TPST-1 and TPST2) have been identified.

Regulation[edit]

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.

Antibody for detection of tyrosine-sulfated epitopes[edit]

In 2006, an article was published in the Journal of Biological Chemistry describing the production and characterization of an antibody called PSG2. This antibody shows exquisite sensitivity and specificity for epitopes containing sulfotyrosine independent of the sequence context.

Sulfation in other amino acids[edit]

See also[edit]

References[edit]

  1. ^ Tyrosine-O-sulfate in a peptide from fibrinogen. F. R. Bettelheim, J. Am. Chem. Soc., 1954, 76 (10), pp 2838–2839, doi:10.1021/ja01639a073