Abstract:
:The sulfoconjugation of tyrosyl residues is a widespread post-translational modification of biologically active proteins and peptides. The rat liver Golgi enzyme tyrosylprotein sulfotransferase has previously been shown to catalyze the transfer of a sulfate moiety from 5'-phosphoadenosine-3'-phosphosulfate to the synthetic acidic polymer poly(Glu6, Ala3, Tyr1) (EAY). In this study, we further characterized the biochemical properties and the substrate specificity of rat liver tyrosylprotein sulfotransferase using a variety of synthetic peptides, including EAY, tert-butoxycarbonylcholecystokinin-8 (Boc-CCK), and two carboxy terminal peptide fragments of complement component C4. The data demonstrate that all substrates can be sulfated by an isolated Golgi membrane fraction. In addition, Boc-CCK was also found to be sulfated by a cytosolic sulfotransferase. Using an enriched Golgi fraction, rat liver tyrosylprotein sulfotransferase sulfation of Boc-CCK displayed a pH optimum between 6.0 and 6.5, was stimulated by 50-150 mM NaCl, and required either Mn2+ or Mg2+ for maximal activity. In contrast, EAY sulfation displayed a pH optimum of 6.7, was not stimulated by NaCl, and required Mn2+ for maximal activity. Both Boc-CCK and EAY sulfation were similarly decreased when the enriched Golgi preparation was preincubated at 45 degrees for varying lengths of time. The particulate tyrosylprotein sulfotransferase could be effectively solubilized by 1% Triton X-100 in the presence of 0.2 M NaCl and anion exchange chromatography of the solubilized enzyme yielded a single peak of Boc-CCK- and EAY-sulfating activities. Rat liver tyrosylprotein sulfotransferase was also shown to sulfate a variety of other acidic and basic synthetic tyrosine-containing polymers, as well as two synthetic peptides of 10 and 16 amino acid residues that corresponding to the C-terminal portion of C4.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Rens-Domiano S,Hortin GL,Roth JAsubject
Has Abstractpub_date
1989-10-01 00:00:00pages
647-53issue
4eissn
0026-895Xissn
1521-0111journal_volume
36pub_type
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journal_title:Molecular pharmacology
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