The Redox-Active Conopeptide Derived from the Venom Duct Transcriptome of Conus lividus Assists in the Oxidative Folding of Conotoxin

摘要: The tetrapeptides Li504 and Li520, differing in the modification of 4-trans-hydroxylation proline, are novel conopeptides derived from venom duct transcriptome marine cone snail Conus lividus. These predicted mature peptides homologous to active site motif oxidoreductases that catalyze oxidation, reduction, rearrangement disulfide bonds proteins. estimated reduction potential Li520 is within range potentials oxidoreductases, indicating they may oxidative folding conotoxins. Conformational features include trans configuration Cys1-Pro2/Hyp2 peptide bond with a type 1 turn similar glutaredoxin regulates oxidation cysteine thiols disulfides. Li504- Li520-assisted α-conotoxin ImI confirms improves yield natively folded by concomitantly decreasing non-native isomer thus acts as miniature isomerase. geometry Cys1-Hyp2 shifts between cis configurations form thiol/thiolate form, which deprotonation N-terminal residue. Hydrogen bonding hydroxyl group 4-trans-hydroxyproline interpeptide chain unit mixed play vital role shifting configuration. conopeptide together other species constitute new family "redox-active" integral components machinery