General Information of This Target
Target ID
BTDT10146
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-6/alpha-3-beta-2-beta-3
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    Alpha-conotoxin PeIA IC50
3.8 nM
[1- 9]
 Toxin Info    Alpha-conotoxin PnIA IC50
11 nM
[10- 22]
 Toxin Info    Alpha-conotoxin PeIA IC50
11.1 - 17.2 nM
[1- 9]
 Toxin Info    Alpha-conotoxin TxIB IC50
28.4 nM
[19- 24]
 Toxin Info    Alpha-conotoxin Vc1a IC50
140 nM
[8- 40]
 Toxin Info    Alpha-conotoxin OmIA IC50
201 nM
[19- 43]
 Toxin Info    Alpha-conotoxin GVIIIB IC50
˜1 μM
[44], [45]
 Toxin Info    Alpha-conotoxin CIC IC50
0.94 μM
[46], [47]
References
Ref 1 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 2 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 3 -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 4 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 5 -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 6 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 7 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 8 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 9 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 10 New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry. 1994 Aug 16;33(32):9523-9. doi: 10.1021/bi00198a018.
Ref 11 Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray, matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry. J Mass Spectrom. 1999 Apr;34(4):447-54. doi: 10.1002/(SICI)1096-9888(199904)34:4<447::AID-JMS801>3.0.CO;2-1.
Ref 12 Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity. Biochemistry. 1999 Nov 2;38(44):14542-8. doi: 10.1021/bi991252j.
Ref 13 Identification of residues that confer alpha-conotoxin-PnIA sensitivity on the alpha 3 subunit of neuronal nicotinic acetylcholine receptors. J Pharmacol Exp Ther. 2003 Aug;306(2):664-70. doi: 10.1124/jpet.103.051656. Epub 2003 May 6.
Ref 14 Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic acetylcholine receptor. J Biol Chem. 2005 Aug 26;280(34):30460-8. doi: 10.1074/jbc.M504229200. Epub 2005 Jun 1.
Ref 15 AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J. 2007 Aug 22;26(16):3858-67. doi: 10.1038/sj.emboj.7601785. Epub 2007 Jul 26.
Ref 16 Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives. J Biol Chem. 2009 Apr 3;284(14):9498-512. doi: 10.1074/jbc.M806136200. Epub 2009 Jan 8.
Ref 17 Nicotinic acetylcholine receptors in dorsal root ganglion neurons include the 64* subtype. FASEB J. 2012 Feb;26(2):917-26. doi: 10.1096/fj.11-195883. Epub 2011 Oct 24.
Ref 18 Hydrophobic residues at position 10 of -conotoxin PnIA influence subtype selectivity between 7 and 32 neuronal nicotinic acetylcholine receptors. Biochem Pharmacol. 2014 Oct 15;91(4):534-42. doi: 10.1016/j.bcp.2014.07.025. Epub 2014 Aug 5.
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 -Conotoxins Enhance both the In Vivo Suppression of Ehrlich carcinoma Growth and In Vitro Reduction in Cell Viability Elicited by Cyclooxygenase and Lipoxygenase Inhibitors. Mar Drugs. 2020 Apr 7;18(4):193. doi: 10.3390/md18040193.
Ref 21 The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus. Structure. 1996 Apr 15;4(4):417-23. doi: 10.1016/s0969-2126(96)00047-0.
Ref 22 Posttranslational modifications of -conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding. RSC Med Chem. 2021 Jul 26;12(9):1574-1584. doi: 10.1039/d1md00182e. eCollection 2021 Sep 23.
Ref 23 Characterization of a novel -conotoxin from conus textile that selectively targets 6/323 nicotinic acetylcholine receptors. J Biol Chem. 2013 Jan 11;288(2):894-902. doi: 10.1074/jbc.M112.427898. Epub 2012 Nov 26.
Ref 24 Effects of Cyclization on Activity and Stability of -Conotoxin TxIB. Mar Drugs. 2020 Mar 29;18(4):180. doi: 10.3390/md18040180.
Ref 25 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 26 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 27 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 28 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 29 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 30 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 31 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 32 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 33 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 34 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 35 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 36 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 37 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 38 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 39 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 40 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.
Ref 41 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 42 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 43 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 44 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 45 S-conotoxin GVIIIB potently and selectively blocks 910 nicotinic acetylcholine receptors. Biochem Pharmacol. 2015 Aug 15;96(4):349-56. doi: 10.1016/j.bcp.2015.06.007. Epub 2015 Jun 11.
Ref 46 Comparative Venomics Reveals the Complex Prey Capture Strategy of the Piscivorous Cone Snail Conus catus. J Proteome Res. 2015 Oct 2;14(10):4372-81. doi: 10.1021/acs.jproteome.5b00630. Epub 2015 Sep 10.
Ref 47 Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel -Conotoxin with an Extended N-Terminal Tail. Mar Drugs. 2021 Mar 2;19(3):141. doi: 10.3390/md19030141.
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