General Information of This Target
Target ID
BTDT10127
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-3-beta-4
Target Bioclass
Receptor
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N.A.
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Elevenin-Vc1 Effect . [1], [2], [3]
 Toxin Info    Alpha-conotoxin Pu14.1 Inhibition rate . [4]
 Toxin Info    Alpha-conotoxin TxID IC50
3.6 - 18.38 nM
[5], [6], [7], [8]
 Toxin Info    Alpha-conotoxin PeIA IC50
3.7 nM
[9- 17]
 Toxin Info    Alpha-conotoxin OmIA IC50
160 nM
[18], [19], [20], [21]
 Toxin Info    Alpha-conotoxin PeIA IC50
0.480 - 1.5 μM
[9- 17]
 Toxin Info    Alpha-conotoxin G1.5 IC50
1.928 μM
[22], [23]
 Toxin Info    Alpha-conotoxin Vc1a IC50
4.2 μM
[16- 39]
References
Ref 1 Diversity of conotoxin gene superfamilies in the venomous snail, Conus victoriae. PLoS One. 2014 Feb 5;9(2):e87648. doi: 10.1371/journal.pone.0087648. eCollection 2014.
Ref 2 Hormone-like peptides in the venoms of marine cone snails. Gen Comp Endocrinol. 2017 Apr 1;244:11-18. doi: 10.1016/j.ygcen.2015.07.012. Epub 2015 Aug 22.
Ref 3 Characterisation of Elevenin-Vc1 from the Venom of Conus victoriae: A Structural Analogue of -Conotoxins. Mar Drugs. 2023 Jan 25;21(2):81. doi: 10.3390/md21020081.
Ref 4 A new subfamily of conotoxins belonging to the A-superfamily. Peptides. 2010 Nov;31(11):2009-16. doi: 10.1016/j.peptides.2010.07.011. Epub 2010 Aug 4.
Ref 5 Characterization of a novel -conotoxin TxID from Conus textile that potently blocks rat 34 nicotinic acetylcholine receptors. J Med Chem. 2013 Dec 12;56(23):9655-63. doi: 10.1021/jm401254c. Epub 2013 Nov 22.
Ref 6 -Conotoxin [S9A]TxID Potently Discriminates between 34 and 6/34 Nicotinic Acetylcholine Receptors. J Med Chem. 2017 Jul 13;60(13):5826-5833. doi: 10.1021/acs.jmedchem.7b00546. Epub 2017 Jun 21.
Ref 7 Single Amino Acid Substitution in -Conotoxin TxID Reveals a Specific 34 Nicotinic Acetylcholine Receptor Antagonist. J Med Chem. 2018 Oct 25;61(20):9256-9265. doi: 10.1021/acs.jmedchem.8b00967. Epub 2018 Oct 9.
Ref 8 Effect of Methionine Oxidation and Substitution of -Conotoxin TxID on 34 Nicotinic Acetylcholine Receptor. Mar Drugs. 2018 Jun 20;16(6):215. doi: 10.3390/md16060215.
Ref 9 A novel alpha-conotoxin, PeIA, cloned from Conus pergrandis, discriminates between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors. J Biol Chem. 2005 Aug 26;280(34):30107-12. doi: 10.1074/jbc.M504102200. Epub 2005 Jun 27.
Ref 10 Structure and activity of alpha-conotoxin PeIA at nicotinic acetylcholine receptor subtypes and GABA(B) receptor-coupled N-type calcium channels. J Biol Chem. 2011 Mar 25;286(12):10233-7. doi: 10.1074/jbc.M110.196170. Epub 2011 Jan 20.
Ref 11 -Conotoxin PeIA[S9H,V10A,E14N] potently and selectively blocks 623 versus 64 nicotinic acetylcholine receptors. Mol Pharmacol. 2012 Nov;82(5):972-82. doi: 10.1124/mol.112.080853. Epub 2012 Aug 22.
Ref 12 Positional scanning mutagenesis of -conotoxin PeIA identifies critical residues that confer potency and selectivity for 6/323 and 32 nicotinic acetylcholine receptors. J Biol Chem. 2013 Aug 30;288(35):25428-25439. doi: 10.1074/jbc.M113.482059. Epub 2013 Jul 11.
Ref 13 -Conotoxins Identify the 34* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells. Mol Pharmacol. 2015 Nov;88(5):881-93. doi: 10.1124/mol.115.100982. Epub 2015 Sep 1.
Ref 14 Correction to "-Conotoxins Identify the 34* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells". Mol Pharmacol. 2016 Feb;89(2):322. doi: 10.1124/mol.115.100982err.
Ref 15 Inhibition of cholinergic pathways in Drosophila melanogaster by -conotoxins. FASEB J. 2015 Mar;29(3):1011-8. doi: 10.1096/fj.14-262733. Epub 2014 Dec 2.
Ref 16 Dimerization of -Conotoxins as a Strategy to Enhance the Inhibition of the Human 7 and 910 Nicotinic Acetylcholine Receptors. J Med Chem. 2020 Mar 26;63(6):2974-2985. doi: 10.1021/acs.jmedchem.9b01536. Epub 2020 Mar 17.
Ref 17 Computational and Functional Mapping of Human and Rat 64 Nicotinic Acetylcholine Receptors Reveals Species-Specific Ligand-Binding Motifs. J Med Chem. 2021 Feb 11;64(3):1685-1700. doi: 10.1021/acs.jmedchem.0c01973. Epub 2021 Feb 1.
Ref 18 Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors. J Biol Chem. 2006 Aug 25;281(34):24678-86. doi: 10.1074/jbc.M602969200. Epub 2006 Jun 27.
Ref 19 Species specificity of rat and human 7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists. Neuropharmacology. 2018 Sep 1;139:226-237. doi: 10.1016/j.neuropharm.2018.07.019. Epub 2018 Jul 17.
Ref 20 Unique Pharmacological Properties of -Conotoxin OmIA at 7 nAChRs. Front Pharmacol. 2021 Dec 8;12:803397. doi: 10.3389/fphar.2021.803397. eCollection 2021.
Ref 21 Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist alpha-conotoxin OmIA that discriminates alpha3 vs. alpha6 nAChR subtypes. Biochem Biophys Res Commun. 2006 Jun 23;345(1):248-54. doi: 10.1016/j.bbrc.2006.04.099. Epub 2006 Apr 27.
Ref 22 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 23 Globular and ribbon isomers of Conus geographus -conotoxins antagonize human nicotinic acetylcholine receptors. Biochem Pharmacol. 2021 Aug;190:114638. doi: 10.1016/j.bcp.2021.114638. Epub 2021 May 29.
Ref 24 A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry. 2003 Jun 10;42(22):6904-11. doi: 10.1021/bi034043e.
Ref 25 Determining sequences and post-translational modifications of novel conotoxins in Conus victoriae using cDNA sequencing and mass spectrometry. J Mass Spectrom. 2004 May;39(5):548-57. doi: 10.1002/jms.624.
Ref 26 A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves. Neuroreport. 2005 Apr 4;16(5):479-83. doi: 10.1097/00001756-200504040-00012.
Ref 27 Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17880-4. doi: 10.1073/pnas.0608715103. Epub 2006 Nov 13.
Ref 28 Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins?. Mol Pharmacol. 2007 Dec;72(6):1406-10. doi: 10.1124/mol.107.040568. Epub 2007 Sep 5.
Ref 29 Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation. J Neurosci. 2008 Oct 22;28(43):10943-51. doi: 10.1523/JNEUROSCI.3594-08.2008.
Ref 30 Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for activity at the alpha9alpha10 nicotinic acetylcholine receptor. J Biol Chem. 2009 Jul 24;284(30):20275-84. doi: 10.1074/jbc.M109.015339. Epub 2009 May 15.
Ref 31 Determination of the -conotoxin Vc1.1 binding site on the 910 nicotinic acetylcholine receptor. J Med Chem. 2013 May 9;56(9):3557-67. doi: 10.1021/jm400041h. Epub 2013 Apr 29.
Ref 32 Structure-Activity Studies of Cysteine-Rich -Conotoxins that Inhibit High-Voltage-Activated Calcium Channels via GABA(B) Receptor Activation Reveal a Minimal Functional Motif. Angew Chem Int Ed Engl. 2016 Apr 4;55(15):4692-6. doi: 10.1002/anie.201600297. Epub 2016 Mar 7.
Ref 33 Cyclic analogues of -conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain. Br J Pharmacol. 2018 Jun;175(12):2384-2398. doi: 10.1111/bph.14115. Epub 2018 Feb 13.
Ref 34 The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1. J Biol Chem. 2006 Aug 11;281(32):23254-63. doi: 10.1074/jbc.M604550200. Epub 2006 Jun 5.
Ref 35 The engineering of an orally active conotoxin for the treatment of neuropathic pain. Angew Chem Int Ed Engl. 2010 Sep 3;49(37):6545-8. doi: 10.1002/anie.201000620.
Ref 36 Dicarba -conotoxin Vc1.1 analogues with differential selectivity for nicotinic acetylcholine and GABAB receptors. ACS Chem Biol. 2013 Aug 16;8(8):1815-21. doi: 10.1021/cb4002393. Epub 2013 Jun 17.
Ref 37 Racemic and quasi-racemic X-ray structures of cyclic disulfide-rich peptide drug scaffolds. Angew Chem Int Ed Engl. 2014 Oct 13;53(42):11236-41. doi: 10.1002/anie.201406563. Epub 2014 Aug 28.
Ref 38 Less is More: Design of a Highly Stable Disulfide-Deleted Mutant of Analgesic Cyclic -Conotoxin Vc1.1. Sci Rep. 2015 Aug 20;5:13264. doi: 10.1038/srep13264.
Ref 39 Structure-Activity Studies Reveal the Molecular Basis for GABA(B)-Receptor Mediated Inhibition of High Voltage-Activated Calcium Channels by -Conotoxin Vc1.1. ACS Chem Biol. 2018 Jun 15;13(6):1577-1587. doi: 10.1021/acschembio.8b00190. Epub 2018 May 25.
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