title: Bromocontryphan: post-translational bromination of tryptophan.
abstract: We demonstrate that post-translational bromination of a tryptophan residue occurs in the biologically active octapeptide bromocontryphan, purified and characterized from Conus radiatus venom. Clones encoding bromocontryphan were identified from a cDNA library made from C. radiatus venom ducts. The mRNA sequence obtained predicts a prepropeptide which has the mature peptide sequence at the C-terminal end, with the L-6-bromotryptophan residue encoded by UGG, the Trp codon. These data provide the first direct evidence for post-translational bromination of a polypeptide which is translated through the normal cellular machinery. In addition to bromination, the peptide, which induces a "stiff tail" syndrome in mice, has several other modifications as shown by the sequence [Formula: See Text] in which Hyp = hydroxyproline. Asterisks indicate post-translational modifications (left to right): proteolytic cleavage at the N-terminus; hydroxylation of Pro3; epimerization of Trp4; bromination of Trp7, and C-terminal amidation. Bromocontryphan appears to have the highest density of post-translational modifications known among gene-encoded polypeptides. The overall result is a molecule which closely resembles marine natural products produced through specialized biosynthetic pathways comprising many enzyme-catalyzed steps.
authors.affiliation: Marine Science Institute, University of the Philippines, Diliman, Quezon City, Philippines.
authors.forename: E C
authors.initials: EC
authors.lastname: Jimenez
authors.forename: A G
authors.initials: AG
authors.lastname: Craig
authors.forename: M
authors.initials: M
authors.lastname: Watkins
authors.forename: D R
authors.initials: DR
authors.lastname: Hillyard
authors.forename: W R
authors.initials: WR
authors.lastname: Gray
authors.forename: J
authors.initials: J
authors.lastname: Gulyas
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: L J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry* / Q000633:toxicity; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000633:toxicity; D014364:Tryptophan
chemical_list: D018076:DNA, Complementary; D008978:Mollusk Venoms; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C102355:contryphan; D014364:Tryptophan