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Open AccessArticle

Characterisation of a Novel A-Superfamily Conotoxin

Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD 4878, Australia
Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia
Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Nußbaumstraße 26, 80336 Munich, Germany
Institut des Biomolécules Max Mousseron, UMR 5247, Université de Montpellier, CNRS, 34095 Montpellier, France
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(5), 128;
Received: 3 May 2020 / Revised: 15 May 2020 / Accepted: 18 May 2020 / Published: 20 May 2020
(This article belongs to the Special Issue Animal Venoms–Curse or Cure?)
Conopeptides belonging to the A-superfamily from the venomous molluscs, Conus, are typically α-conotoxins. The α-conotoxins are of interest as therapeutic leads and pharmacological tools due to their selectivity and potency at nicotinic acetylcholine receptor (nAChR) subtypes. Structurally, the α-conotoxins have a consensus fold containing two conserved disulfide bonds that define the two-loop framework and brace a helical region. Here we report on a novel α-conotoxin Pl168, identified from the transcriptome of Conus planorbis, which has an unusual 4/8 loop framework. Unexpectedly, NMR determination of its three-dimensional structure reveals a new structural type of A-superfamily conotoxins with a different disulfide-stabilized fold, despite containing the conserved cysteine framework and disulfide connectivity of classical α-conotoxins. The peptide did not demonstrate activity on a range of nAChRs, or Ca2+ and Na+ channels suggesting that it might represent a new pharmacological class of conotoxins. View Full-Text
Keywords: conopeptide; NMR spectroscopy; disulfide framework conopeptide; NMR spectroscopy; disulfide framework
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Wilson, D.T.; Bansal, P.S.; Carter, D.A.; Vetter, I.; Nicke, A.; Dutertre, S.; Daly, N.L. Characterisation of a Novel A-Superfamily Conotoxin. Biomedicines 2020, 8, 128.

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