General Information of This Target
Target ID
BTDT10123
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-3-beta-2
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 PiXXA Inhibition rate . [4]
 Toxin Info    Alpha-conotoxin Lt28.1 Inhibition rate
19.4 %
[5]
 Toxin Info    Alpha-conotoxin PnIA IC50
0.7 nM
[6- 18]
 Toxin Info    Alpha-conotoxin GID IC50
3.1 - 5.1 nM
[10- 23]
 Toxin Info    Alpha-conotoxin PeIA IC50
6.1 nM
[24- 32]
 Toxin Info    Alpha-conotoxin PnIA IC50
7.68 nM
[6- 18]
 Toxin Info    Alpha-conotoxin PeIA IC50
9.7 - 97.5 nM
[24- 32]
 Toxin Info    Alpha-conotoxin OmIA IC50
11 nM
[15- 35]
 Toxin Info    Alpha-conotoxin ArIA IC50
18 nM
[36], [37]
 Toxin Info    Alpha-conotoxin Lt1.3 b IC50
44.8 nM
[38]
 Toxin Info    Alpha-conotoxin ArIA IC50
60.1 nM
[36], [37]
 Toxin Info    Alpha-conotoxin Vc1.2 IC50
75 nM
[39]
 Toxin Info    Alpha-conotoxin ViIA IC50
845.5 nM
[40]
 Toxin Info    Alpha-conotoxin GVIIIB IC50
˜1 μM
[19- 41]
 Toxin Info    Alpha-elapitoxin-Bc2a IC50
2.9 μM
[42]
 Toxin Info    Alpha-conotoxin CIC IC50
3.51 μM
[43], [44]
 Toxin Info    Alpha-conotoxin Vc1a IC50
5.5 - 7.3 μM
[31- 60]
 Toxin Info    Three-finger toxin 3b IC50
12.6 μM
[61]
 Toxin Info    Fulditoxin IC50
12.6 μM
[61], [62], [63]
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 D-Conotoxins in Species of the Eastern Pacific: The Case of Conus princeps from Mexico. Toxins (Basel). 2019 Jul 12;11(7):405. doi: 10.3390/toxins11070405.
Ref 5 Cloning, expression and functional characterization of a D-superfamily conotoxin Lt28.1 with previously undescribed cysteine pattern. Peptides. 2017 Aug;94:64-70. doi: 10.1016/j.peptides.2017.06.008. Epub 2017 Jun 27.
Ref 6 New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry. 1994 Aug 16;33(32):9523-9. doi: 10.1021/bi00198a018.
Ref 7 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 8 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 9 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 10 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 11 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 12 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 13 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 14 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 15 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 16 -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 17 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 18 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 19 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 20 Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence. J Biol Chem. 2003 Jan 31;278(5):3137-44. doi: 10.1074/jbc.M210280200. Epub 2002 Nov 4.
Ref 21 Inhibition of neuronal nicotinic acetylcholine receptor subtypes by alpha-Conotoxin GID and analogues. J Biol Chem. 2009 Feb 20;284(8):4944-51. doi: 10.1074/jbc.M804950200. Epub 2008 Dec 19.
Ref 22 Design and synthesis of -conotoxin GID analogues as selective 42 nicotinic acetylcholine receptor antagonists. Biopolymers. 2014 Jan;102(1):78-87. doi: 10.1002/bip.22413.
Ref 23 Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8100-E8109. doi: 10.1073/pnas.1703952114. Epub 2017 Sep 5.
Ref 24 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 25 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 26 -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 27 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 28 -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 29 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 30 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 31 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 32 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 33 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 34 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 35 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 36 Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist. Biochemistry. 2007 Jun 5;46(22):6628-38. doi: 10.1021/bi7004202. Epub 2007 May 12.
Ref 37 Alpha-conotoxin Arenatus IB[V11L,V16D] [corrected] is a potent and selective antagonist at rat and human native alpha7 nicotinic acetylcholine receptors. J Pharmacol Exp Ther. 2008 Nov;327(2):529-37. doi: 10.1124/jpet.108.142943. Epub 2008 Jul 29.
Ref 38 Cloning, Synthesis and Functional Characterization of a Novel -Conotoxin Lt1.3. Mar Drugs. 2018 Mar 31;16(4):112. doi: 10.3390/md16040112.
Ref 39 Embryonic toxin expression in the cone snail Conus victoriae: primed to kill or divergent function?. J Biol Chem. 2011 Jun 24;286(25):22546-57. doi: 10.1074/jbc.M110.217703. Epub 2011 Apr 19.
Ref 40 A novel 4/6-type alpha-conotoxin ViIA selectively inhibits nAchR 32 subtype. Acta Biochim Biophys Sin (Shanghai). 2015 Dec;47(12):1023-8. doi: 10.1093/abbs/gmv105. Epub 2015 Oct 28.
Ref 41 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 42 Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors. Biochem J. 2019 Apr 26;476(8):1285-1302. doi: 10.1042/BCJ20180909.
Ref 43 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 44 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.
Ref 45 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 46 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 47 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 48 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 49 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 50 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 51 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 52 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 53 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 54 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 55 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 56 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 57 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 58 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 59 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 60 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 61 The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms. BMC Genomics. 2013 Aug 2;14:531. doi: 10.1186/1471-2164-14-531.
Ref 62 Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms. G3 (Bethesda). 2015 Sep 9;5(11):2375-82. doi: 10.1534/g3.115.020578.
Ref 63 Fulditoxin, representing a new class of dimeric snake toxins, defines novel pharmacology at nicotinic ACh receptors. Br J Pharmacol. 2020 Apr;177(8):1822-1840. doi: 10.1111/bph.14954. Epub 2020 Feb 9.
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