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Literature summary for 2.8.2.20 extracted from

  • Yeoh, S.; Bayliss, R.
    New tools for evaluating protein tyrosine sulfation and carbohydrate sulfation (2018), Biochem. J., 475, 3035-3037 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
human TPST1 in complex with adenosine 3'-5' diphosphate (PAP) and two different substrate peptides (PDB codes 5WRI and 5WRJ) Homo sapiens

General Stability

General Stability Organism
TPST isozymes are stabilised by cofactors such as CoA Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information biochemical screening of a library of kinase inhibitors reveals that compounds that target RAF kinases may also be repurposed to inhibit sulfotransferases. Oxindole-derived RAF kinase inhibitors are among the top 10 hits against TPST1. Synthetic fluorescent substrates, fluorescein-tagged hexasaccharide glycans, or FAM-labelled peptides derived from physiological target proteins are used in microfluidics-based mobility shift assay (MSA) to carry out real-time analysis of the enzyme kinetics of TPST 1/2. Docking analysis and mode of action in sulfotransferases show that the RAF kinase inhibitors do not simply compete with the substrate molecule PAPS. Some of the compounds are predicted to bind across the peptide/glycan and PAPS-binding sites Homo sapiens
rottlerin a natural product that has activity against a broad set of biological targets including kinases, inhibits both TPST1 and heparan sulfate 2-O-sulfotransferase (HS2ST). Rotterlin is predicted to dock to the PAPS-binding site of HS2ST and the peptide-binding site of TPST1 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens O60507
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information synthetic fluorescent substrates, fluorescein-tagged hexasaccharide glycans, or FAM-labelled peptides derived from physiological target proteins are used in microfluidics-based mobility shift assay (MSA) to carry out real-time analysis of the enzyme kinetics of TPST 1/2 Homo sapiens ?
-
-

Synonyms

Synonyms Comment Organism
TPST1
-
Homo sapiens
tyrosylprotein sulfotransferases 1
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Homo sapiens

General Information

General Information Comment Organism
evolution the catalytic domain of sulfotransferases is unrelated to that of protein kinases, and moreover, the way in which the substrates are held are different. Protein kinases have a deep cleft into which ATP binds and the protein substrate binds to the surface proximal to this cleft. ATP is held in an orientation that buries the adenine base. In contrast, the active site of sulfotransferase comprises a tunnel with the binding sites for PAPS and peptide/glycan substrate is at either end, PAPS binds to the active site of sulfotransferases in an orientation that exposes the adenine base to solvent Homo sapiens
metabolism biological sulfation (also called sulfonation) is a widespread covalent chemical modification of biomolecules by the addition of a sulfonyl group (SO3-). Inorganic sulfate is made available for incorporation into biomolecules in the form of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) through a process in which ATP is first sulfated by the ATP sulfurylase enzyme to generate adenosine 5'-phosphosulfate, which is then phosphorylated on the 3' position of the ribose ring to generate PAPS. Sulfation is carried out by a class of enzymes called sulfotransferases Homo sapiens
physiological function about 7% of mammalian proteins are sulfated on tyrosine residues. Many chemokine receptors are tyrosine sulfated in their N-terminal regions. Sulfation also contributes to the binding of chemokine ligands, such as CCL3 and CCL4. The interactions between other chemokine receptors and their native or pathogenic ligands are also enhanced by sulfation. Antibodies can also be sulfated on tyrosine residues, thus increasing the repertoire of the surface that recognises antigens through a mechanism that mimics the post-translational modification of co-receptors Homo sapiens