General Information of This Target
Target ID
BTDT10104
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-1-beta-1-gamma-delta
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    Long neurotoxin 2 Inhibition constant
2.17 nM
[1], [2]
 Toxin Info    Alpha-conotoxin CIB Inhibition rate . [3], [4]
 Toxin Info    Alpha-conotoxin PeIVA IC50
≤5 nM
[5]
 Toxin Info    Alpha-conotoxin OIVA IC50
0.51 nM
[5], [6]
 Toxin Info    Three-finger toxin A1 IC50
1.4 nM
[7]
 Toxin Info    Alpha-conotoxin PIVA IC50
2.3 nM
[5- 9]
 Toxin Info    Alpha-conotoxin OI IC50
52.1 nM
[10]
 Toxin Info    Alpha-conotoxin OIVB IC50
66 nM
[5- 11]
 Toxin Info    Alpha-conotoxin SI IC50
113 nM
[12- 17]
 Toxin Info    Alpha-conotoxin OIVA IC50
310 nM
[6], [5]
 Toxin Info    Alpha-conotoxin SII IC50
370 nM
[12- 20]
 Toxin Info    Alpha-conotoxin Vc1a IC50
>30 μM
[21- 37]
 Toxin Info    Alpha-conotoxin MilIA IC50
13 μM
[38]
References
Ref 1 Snake venom toxins. The amino acid sequences of toxins b and d from Naja melanoleuca venom. J Biol Chem. 1972 May 10;247(9):2866-71.
Ref 2 Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABA(A) and Nicotinic Acetylcholine Receptors. Toxins (Basel). 2021 Feb 20;13(2):164. doi: 10.3390/toxins13020164.
Ref 3 Evolution of Conus peptide genes: duplication and positive selection in the A-superfamily. J Mol Evol. 2010 Feb;70(2):190-202. doi: 10.1007/s00239-010-9321-7. Epub 2010 Feb 9.
Ref 4 Synthesis, Structure and Biological Activity of CIA and CIB, Two -Conotoxins from the Predation-Evoked Venom of Conus catus. Toxins (Basel). 2018 Jun 1;10(6):222. doi: 10.3390/toxins10060222.
Ref 5 Definition and characterization of the short alphaA-conotoxins: a single residue determines dissociation kinetics from the fetal muscle nicotinic acetylcholine receptor. Biochemistry. 2006 Jan 31;45(4):1304-12. doi: 10.1021/bi052016d.
Ref 6 AlphaA-Conotoxin OIVA defines a new alphaA-conotoxin subfamily of nicotinic acetylcholine receptor inhibitors. Toxicon. 2004 Aug;44(2):207-14. doi: 10.1016/j.toxicon.2004.05.026.
Ref 7 Isolation, characterization, cloning and expression of an alpha-neurotoxin from the venom of the Mexican coral snake Micrurus laticollaris (Squamata: Elapidae). Toxicon. 2013 May;66:64-74. doi: 10.1016/j.toxicon.2013.02.006. Epub 2013 Feb 22.
Ref 8 A new family of Conus peptides targeted to the nicotinic acetylcholine receptor. J Biol Chem. 1995 Sep 22;270(38):22361-7. doi: 10.1074/jbc.270.38.22361.
Ref 9 NMR structure determination of a novel conotoxin, [Pro 7,13] alpha A-conotoxin PIVA. Biochemistry. 1997 Feb 18;36(7):1669-77. doi: 10.1021/bi962301k.
Ref 10 Research into the Bioengineering of a Novel -Conotoxin from the Milked Venom of Conus obscurus. Int J Mol Sci. 2022 Oct 11;23(20):12096. doi: 10.3390/ijms232012096.
Ref 11 A uniquely selective inhibitor of the mammalian fetal neuromuscular nicotinic acetylcholine receptor. J Neurosci. 2005 Jan 19;25(3):732-6. doi: 10.1523/JNEUROSCI.4065-04.2005.
Ref 12 Conopeptides from Conus striatus and Conus textile by cDNA cloning. Peptides. 1999;20(10):1139-44. doi: 10.1016/s0196-9781(99)00116-3.
Ref 13 The A-superfamily of conotoxins: structural and functional divergence. J Biol Chem. 2004 Apr 23;279(17):17596-606. doi: 10.1074/jbc.M309654200. Epub 2003 Dec 30.
Ref 14 Phylogenetic specificity of cholinergic ligands: alpha-conotoxin SI. Biochemistry. 1988 Sep 6;27(18):7102-5. doi: 10.1021/bi00418a065.
Ref 15 Determinants involved in the affinity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors. Biochemistry. 1997 May 27;36(21):6469-74. doi: 10.1021/bi970195w.
Ref 16 Cysteine-Rich -Conotoxin SII Displays Novel Interactions at the Muscle Nicotinic Acetylcholine Receptor. ACS Chem Neurosci. 2022 Apr 20;13(8):1245-1250. doi: 10.1021/acschemneuro.1c00857. Epub 2022 Mar 31.
Ref 17 Solution structure of alpha-conotoxin SI. FEBS Lett. 2000 Jul 7;476(3):287-95. doi: 10.1016/s0014-5793(00)01724-5.
Ref 18 cDNA cloning of two A-superfamily conotoxins from Conus striatus. Toxicon. 2003 Nov;42(6):613-9. doi: 10.1016/j.toxicon.2003.08.005.
Ref 19 Novel alpha- and omega-conotoxins from Conus striatus venom. Biochemistry. 1992 Oct 20;31(41):9919-26. doi: 10.1021/bi00156a009.
Ref 20 Optimizing the connectivity in disulfide-rich peptides: alpha-conotoxin SII as a case study. Anal Biochem. 2005 Mar 1;338(1):48-61. doi: 10.1016/j.ab.2004.10.001.
Ref 21 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 22 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 23 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 24 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 25 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 26 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 27 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 28 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 29 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 30 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 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 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 33 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 34 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 35 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 36 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 37 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 38 Structure-Function Elucidation of a New -Conotoxin, MilIA, from Conus milneedwardsi. Mar Drugs. 2019 Sep 16;17(9):535. doi: 10.3390/md17090535.
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