O-Sulfation is a common post-translational modification of tyrosine residues in eukaryotes, but has not been observed in yeast and prokaryotes. Sulfation is limited to secretory and trans-membrane proteins that have passed the trans-Golgi network, where two membrane-bound tyrosylprotein sulfotransferase enzymes catalyze the transfer of sulfate from adenosine 3’-phosphate5’-phosphosulfate to the tyrosine phenol.

NoHSO3HAv: 80.063
M: 79.9568
Physicochemical properties of O-sulfation that are stored in the modification database of Prot pi (NC: Native charge; H: Relative hydrophobicity; AA: Modified amino acid; Pattern: Regex for sequence-motif recognition).

In-depth mechanism

O-Sulfation is a post-translational modification in which a sulfuryl group is covalently linked tothe hydroxyl group of a tyrosine residue​1–5​. The sulfuryl group must be activated first inorder for the transfer to take place. An active sulfuryl group is formed by the reaction of inorganic sulfate with ATP resulting in adenosine-5’-phosphosulfate (APS) and 3’-phospho-adenosine-5’-phosphosulfate (PAPS). These two molecules are known as universal sulfate donors​1–4​. In fungi and few bacteria PAPS is preferred as donor while in plants, algae and most bacteria APS is preferred [63]. The transfer is catalysed by tyrosylprotein sulfotransferases (TPST) which aremembrane-associated proteins located in the trans-Golgi network​1–3,5​. The mechanism of O-sulfation is shown in figure 28.

Mechanism of O-sulfation. A sulfuryl group is transferred from PAPS onto a tyrosine residue by TPST.

O-Sulfation occurs in higher eukaryotic species. So far it has been observed in all tested mammalian cell lines, but not in prokaryotes or yeast​2​. Thus far, no specific consensus sequence for O-sulfation sites has been reported. However, sulfated tyrosine residues are surrounded by many acidic amino acids residues​2,6​. The function of O-sulfation is unknown for most proteins. The function of the majority of known tyrosine-sulfated proteins seems to be the participation in protein-protein interaction, which is at least partially regulated by the sulfuryl group​1–3​. In general, O-sulfation does not seem to be essential for the proper function. Enzyme activity is reduced in absence, but not entirely eliminated. At the current time, O-sulfation has been observed only in secreted and transmembrane proteins​1,2​. Tyrosine O-sulfation increases the molecular mass of the modified protein by 80 Da​5​. In addition, the pKa value is lowered from 10.07 of tyrosine to -3.88 for phenylsulfate. Furthermore, the possible sites for hydrogen bonds are quadrupled in tyrosine-sulfated proteins​7​.


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