AbbreviationsBLASTbasic local alignment search toolCDAP1‐cyano‐4‐dimethylamino‐pyridinium tetrafluoroborateCSIchemical shift indexDTTdithiothreitolEDTAethylenediaminetetraacetic acidIAMiodoacetamideMALDI‐TOFmatrix assisted laser desorption ionization time‐of‐flightNOEnuclear Overhauser effectPFGpulse field gradientPTHphenylthiohydantoinPTMposttranslational modificationRFradio frequencyRMSDroot‐mean‐square deviationRPreversed phaseSCUBAself‐contained underwater breading apparatusSEsize exclusionTCEPtris(2‐carboxyethyl)phosphineTFAtrifluoroacetic acidTSP3‐(Trimethylsilyl)‐ Propionic acid‐D4, sodium saltWETwater suppression enhanced through T1 effectsIntroductionVenoms from predatory animals are rich sources of disulfide‐constrained peptides and proteins. Cone snails, a genus of venomous predatory marine mollusks, excel at producing highly modified disulfide‐rich peptidic scaffolds . These slow‐moving animals deploy a proboscis that is tipped with a modified radular tooth used to impale their prey (fish, worms, or mollusks) and deliver their venom. Cone snail venom is a complex concoction of hundreds of compounds that act synergistically to immobilize prey . Conotoxins, venom peptides with two or more disulfides, are highly modified by hydroxylation, carboxylation, bromination, glycosylation, epimerization and combinations of these modifications . These modifications can help to increase conotoxin stability and specificity toward their molecular targets . Conotoxins are classified by superfamilies, which are defined by the conserved signal sequences in the precursor proteins of these peptides. Beyond the superfamilies, conotoxins are further grouped according to their pharmacological targets, which include voltage‐gated ion channels (Na+, K+, and Ca2+) and ligand‐gated ion channels (nAChR, AMPAR, GABAR and 5‐HT3R) .Conotoxins
Febs Journal – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
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