General Information of This Target
Target ID
BTDT10124
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-3-beta-4
Target Bioclass
Receptor
Taxonomy ID
9606
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Elevenin Effect . [1]
 Toxin Info    Elevenin Effect . [2]
 Toxin Info    Alpha-conotoxin Mr1.1 Inhibition rate
60 %
[3], [4], [5]
 Toxin Info    Alpha-conotoxin RegIIA IC50
2.8 nM
[6- 12]
 Toxin Info    Conotoxin Czon1107 IC50
15.7 nM
[13], [14]
 Toxin Info    Alpha-conotoxin PeIA IC50
179 - 230 nM
[15- 23]
References
Ref 1 A Combined Transcriptomics and Proteomics Approach Reveals the Differences in the Predatory and Defensive Venoms of the Molluscivorous Cone Snail Cylinder ammiralis (Caenogastropoda: Conidae). Toxins (Basel). 2021 Sep 10;13(9):642. doi: 10.3390/toxins13090642.
Ref 2 Comparative Venomics of the Cryptic Cone Snail Species Virroconus ebraeus and Virroconus judaeus. Mar Drugs. 2022 Feb 17;20(2):149. doi: 10.3390/md20020149.
Ref 3 From the identification of gene organization of alpha conotoxins to the cloning of novel toxins. Toxicon. 2007 Jun 15;49(8):1135-49. doi: 10.1016/j.toxicon.2007.02.011. Epub 2007 Mar 1.
Ref 4 Chemical synthesis and characterization of two 4/7-conotoxins. Acta Biochim Biophys Sin (Shanghai). 2010 Oct;42(10):745-53. doi: 10.1093/abbs/gmq074. Epub 2010 Aug 27.
Ref 5 Mechanism of Action and Structure-Activity Relationship of -Conotoxin Mr1.1 at the Human 910 Nicotinic Acetylcholine Receptor. J Med Chem. 2022 Dec 22;65(24):16204-16217. doi: 10.1021/acs.jmedchem.2c00494. Epub 2022 Sep 22.
Ref 6 RegIIA: an 4/7-conotoxin from the venom of Conus regius that potently blocks 34 nAChRs. Biochem Pharmacol. 2012 Feb 1;83(3):419-26. doi: 10.1016/j.bcp.2011.11.006. Epub 2011 Nov 16.
Ref 7 Hyperhydroxylation: a new strategy for neuronal targeting by venomous marine molluscs. Prog Mol Subcell Biol. 2006;43:83-103. doi: 10.1007/978-3-540-30880-5_4.
Ref 8 Alanine scan of -conotoxin RegIIA reveals a selective 34 nicotinic acetylcholine receptor antagonist. J Biol Chem. 2015 Jan 9;290(2):1039-48. doi: 10.1074/jbc.M114.605592. Epub 2014 Nov 19.
Ref 9 Molecular Basis for Differential Sensitivity of -Conotoxin RegIIA at Rat and Human Neuronal Nicotinic Acetylcholine Receptors. Mol Pharmacol. 2015 Dec;88(6):993-1001. doi: 10.1124/mol.115.100503. Epub 2015 Oct 5.
Ref 10 Key Structural Determinants in the Agonist Binding Loops of Human 2 and 4 Nicotinic Acetylcholine Receptor Subunits Contribute to 34 Subtype Selectivity of -Conotoxins. J Biol Chem. 2016 Nov 4;291(45):23779-23792. doi: 10.1074/jbc.M116.730804. Epub 2016 Sep 19.
Ref 11 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 12 Rational Design of -Conotoxin RegIIA Analogues Selectively Inhibiting the Human 32 Nicotinic Acetylcholine Receptor through Computational Scanning. ACS Chem Neurosci. 2020 Sep 16;11(18):2804-2811. doi: 10.1021/acschemneuro.0c00293. Epub 2020 Sep 3.
Ref 13 Structure and allosteric activity of a single-disulfide conopeptide from Conus zonatus at human 34 and 7 nicotinic acetylcholine receptors. J Biol Chem. 2020 May 15;295(20):7096-7112. doi: 10.1074/jbc.RA119.012098. Epub 2020 Mar 31.
Ref 14 Single-Disulfide Conopeptide Czon1107, an Allosteric Antagonist of the Human 34 Nicotinic Acetylcholine Receptor. Mar Drugs. 2022 Jul 31;20(8):497. doi: 10.3390/md20080497.
Ref 15 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 16 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 17 -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 18 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 19 -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 20 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 21 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 22 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 23 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.
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