Bromocontryphan: post-translational bromination of tryptophan.
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.
Jimenez
E C
EC
Marine Science Institute, University of the Philippines, Diliman, Quezon City, Philippines.
Craig
A G
AG
Watkins
M
M
Hillyard
D R
DR
Gray
W R
WR
Gulyas
J
J
Rivier
J E
JE
Cruz
L J
LJ
Olivera
B M
BM
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
D018076:DNA, Complementary; D008978:Mollusk Venoms; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C102355:contryphan; D014364:Tryptophan