General Information of This Target
Target ID
BTDT10154
Target Name
Nicotinic acetylcholine receptor (nAChR) alpha-7
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-elapitoxin-Ls2a Dissociation constant
3 nM
[1- 6]
 Toxin Info    Alpha-cobratoxin Dissociation constant
13 - 105 nM
[4- 23]
 Toxin Info    Short neurotoxin 1 Dissociation constant
3 μM
[4- 25]
 Toxin Info    Long neurotoxin Tx-NM3-1 Inhibition constant
4.84 nM
[26]
 Toxin Info    Long neurotoxin Tx-NM2 Inhibition constant
9.47 nM
[26]
 Toxin Info    Long neurotoxin 2 Inhibition constant
26.9 nM
[27], [26]
 Toxin Info    Elevenin-Vc1 Effect . [28], [29], [30]
 Toxin Info    Alpha-conotoxin-like Pu1.2 Inhibition rate . [31], [32]
 Toxin Info    Mu-theraphotoxin-Pn3a Inhibition rate . [33- 38]
 Toxin Info    Alpha-conotoxin ArIA IC50
1.8 nM
[39], [40]
 Toxin Info    Alpha-conotoxin PnIA IC50
4.3 nM
[15- 52]
 Toxin Info    Alpha-conotoxin GID IC50
4.5 - 5.1 nM
[45- 57]
 Toxin Info    Alpha-conotoxin ArIA IC50
6 nM
[39], [40]
 Toxin Info    Candoxin IC50
50 nM
[58], [59], [60]
 Toxin Info    Alpha-elapitoxin-Dpp2d IC50
58 nM
[61]
 Toxin Info    Alpha-conotoxin PnIA IC50
253 nM
[15- 52]
 Toxin Info    Three-finger toxin A1 IC50
400 nM
[62]
 Toxin Info    Alpha-conotoxin RgIA IC50
>10 μM
[63- 75]
 Toxin Info    Alpha-conotoxin MilIA IC50
>10 μM
[76]
 Toxin Info    Alpha-conotoxin G1.5 IC50
1.935 μM
[53- 77]
 Toxin Info    Alpha-conotoxin Lo1a IC50
3.24 μM
[78]
 Toxin Info    Alpha-conotoxin PiXXA IC50
6.2 μM
[79]
 Toxin Info    Three-finger toxin 3b IC50
7 μM
[80]
 Toxin Info    Fulditoxin IC50
7 μM
[80], [81], [82]
References
Ref 1 Complete nucleotide sequences of cDNAs encoding long chain alpha-neurotoxins from sea krait, Laticauda semifasciata. Toxicon. 1999 Jan;37(1):181-5. doi: 10.1016/s0041-0101(98)00181-0.
Ref 2 Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences. Gene. 2003 Aug 14;313:111-8. doi: 10.1016/s0378-1119(03)00637-1.
Ref 3 The primary structure of the toxin Laticauda semifasciata III, a weak and reversibly acting neurotoxin from the venom of a sea snake, Laticauda semifasciata. Biochem J. 1974 Aug;141(2):389-400. doi: 10.1042/bj1410389.
Ref 4 Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. doi: 10.1074/jbc.272.39.24279.
Ref 5 Neurotoxins from snake venoms and -conotoxin ImI inhibit functionally active ionotropic -aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. doi: 10.1074/jbc.M115.648824. Epub 2015 Jul 28.
Ref 6 Solution structure of LSIII, a long neurotoxin from the venom of Laticauda semifasciata. Biochemistry. 1996 Jan 16;35(2):418-26. doi: 10.1021/bi9520287.
Ref 7 Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification. J Biol Chem. 2008 May 23;283(21):14571-80. doi: 10.1074/jbc.M802085200. Epub 2008 Apr 1.
Ref 8 Fluorescein isothiocyanate-labeled alpha-cobratoxin. Biochemical characterization and interaction with acetylcholine receptor from Electrophorus electricus. J Biol Chem. 1980 Aug 10;255(15):7326-32.
Ref 9 The sites of neurotoxicity in alpha-cobratoxin. J Biol Chem. 1983 Jul 25;258(14):8714-22.
Ref 10 alpha-Cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons. Eur J Pharmacol. 1990 Dec 4;191(3):505-6. doi: 10.1016/0014-2999(90)94190-9.
Ref 11 alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;352(6):646-52. doi: 10.1007/BF00171324.
Ref 12 Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo. Neurochem Int. 1998 Oct;33(4):307-12. doi: 10.1016/s0197-0186(98)00033-3.
Ref 13 Variability among the sites by which curaremimetic toxins bind to torpedo acetylcholine receptor, as revealed by identification of the functional residues of alpha-cobratoxin. J Biol Chem. 1999 Dec 3;274(49):34851-8. doi: 10.1074/jbc.274.49.34851.
Ref 14 Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal alpha 7-nicotinic acetylcholine receptor. J Biol Chem. 2000 Sep 22;275(38):29594-601. doi: 10.1074/jbc.M909746199.
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 Experimentally based model of a complex between a snake toxin and the alpha 7 nicotinic receptor. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3216-21. doi: 10.1073/pnas.042699899. Epub 2002 Feb 26.
Ref 17 Three-dimensional structure of the "long" neurotoxin from cobra venom. Proc Natl Acad Sci U S A. 1980 May;77(5):2400-4. doi: 10.1073/pnas.77.5.2400.
Ref 18 The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution. J Biol Chem. 1991 Nov 15;266(32):21530-6. doi: 10.2210/pdb2ctx/pdb.
Ref 19 Rapid determination and NMR assignments of antiparallel sheets and helices of a scorpion and a cobra toxin. Int J Pept Protein Res. 1990 Sep;36(3):227-30. doi: 10.1111/j.1399-3011.1990.tb00971.x.
Ref 20 Alpha-cobratoxin: proton NMR assignments and solution structure. Biochemistry. 1992 May 26;31(20):4867-75. doi: 10.1021/bi00135a018.
Ref 21 NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica. J Biol Chem. 2002 Oct 4;277(40):37439-45. doi: 10.1074/jbc.M205483200. Epub 2002 Jul 19.
Ref 22 Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors. EMBO J. 2005 Apr 20;24(8):1512-22. doi: 10.1038/sj.emboj.7600620. Epub 2005 Mar 24.
Ref 23 Dimeric -cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. J Biol Chem. 2012 Feb 24;287(9):6725-34. doi: 10.1074/jbc.M111.322313. Epub 2012 Jan 5.
Ref 24 Three-dimensional solution structure of a curaremimetic toxin from Naja nigricollis venom: a proton NMR and molecular modeling study. Biochemistry. 1992 Nov 24;31(46):11335-47. doi: 10.1021/bi00161a011.
Ref 25 Motions and structural variability within toxins: implication for their use as scaffolds for protein engineering. Protein Sci. 2003 Feb;12(2):266-77. doi: 10.1110/ps.0227703.
Ref 26 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 27 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 28 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 29 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 30 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 31 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 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 Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883.
Ref 34 Corrigendum: Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 May 26;7:46816. doi: 10.1038/srep46816.
Ref 35 Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen. Pain. 2019 Aug;160(8):1766-1780. doi: 10.1097/j.pain.0000000000001567.
Ref 36 Chemical Synthesis, Proper Folding, Na(v) Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins (Basel). 2019 Jun 21;11(6):367. doi: 10.3390/toxins11060367.
Ref 37 Spider Venom Peptide Pn3a Inhibition of Primary Afferent High Voltage-Activated Calcium Channels. Front Pharmacol. 2021 Jan 28;11:633679. doi: 10.3389/fphar.2020.633679. eCollection 2020.
Ref 38 -Theraphotoxin Pn3a inhibition of Ca(V)3.3 channels reveals a novel isoform-selective drug binding site. Elife. 2022 Jul 20;11:e74040. doi: 10.7554/eLife.74040.
Ref 39 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 40 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 41 New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry. 1994 Aug 16;33(32):9523-9. doi: 10.1021/bi00198a018.
Ref 42 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 43 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 44 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 45 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 46 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 47 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 48 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 49 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 50 -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 51 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 52 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 53 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 54 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 55 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 56 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 57 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 58 Candoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (alphabetagammadelta ) but a poorly reversible antagonist of neuronal alpha 7 nicotinic acetylcholine receptors. J Biol Chem. 2002 May 17;277(20):17811-20. doi: 10.1074/jbc.M111152200. Epub 2002 Mar 7.
Ref 59 Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus). Br J Pharmacol. 2003 Jun;139(4):832-44. doi: 10.1038/sj.bjp.0705299.
Ref 60 Crystallization and preliminary X-ray analysis of candoxin, a novel reversible neurotoxin from the Malayan krait Bungarus candidus. Acta Crystallogr D Biol Crystallogr. 2003 Mar;59(Pt 3):584-6. doi: 10.1107/s0907444903001094. Epub 2003 Feb 21.
Ref 61 Isolation and structural and pharmacological characterization of -elapitoxin-Dpp2d, an amidated three finger toxin from black mamba venom. Biochemistry. 2014 Jun 17;53(23):3758-66. doi: 10.1021/bi5004475. Epub 2014 Jun 5.
Ref 62 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 63 Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR. Biochemistry. 2006 Feb 7;45(5):1511-7. doi: 10.1021/bi0520129.
Ref 64 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 65 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 66 Effects of cyclization on stability, structure, and activity of -conotoxin RgIA at the 910 nicotinic acetylcholine receptor and GABA(B) receptor. J Med Chem. 2011 Oct 13;54(19):6984-92. doi: 10.1021/jm201060r. Epub 2011 Sep 15.
Ref 67 Molecular basis for the differential sensitivity of rat and human 910 nAChRs to -conotoxin RgIA. J Neurochem. 2012 Sep;122(6):1137-44. doi: 10.1111/j.1471-4159.2012.07867.x. Epub 2012 Aug 3.
Ref 68 -conotoxin RgIA protects against the development of nerve injury-induced chronic pain and prevents both neuronal and glial derangement. Pain. 2014 Oct;155(10):1986-95. doi: 10.1016/j.pain.2014.06.023. Epub 2014 Jul 5.
Ref 69 Molecular interaction of -conotoxin RgIA with the rat 910 nicotinic acetylcholine receptor. Mol Pharmacol. 2015 May;87(5):855-64. doi: 10.1124/mol.114.096511. Epub 2015 Mar 4.
Ref 70 Corrections to "Molecular interaction of -conotoxin RgIA with the rat 910 nicotinic acetylcholine receptor". Mol Pharmacol. 2016 Oct;90(4):415-7. doi: 10.1124/mol.114.096511err.
Ref 71 Inhibition of 910 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1825-E1832. doi: 10.1073/pnas.1621433114. Epub 2017 Feb 21.
Ref 72 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 73 The three-dimensional structure of the analgesic alpha-conotoxin, RgIA. FEBS Lett. 2008 Mar 5;582(5):597-602. doi: 10.1016/j.febslet.2008.01.027. Epub 2008 Jan 31.
Ref 74 Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR: structure and identification of key receptor-binding residues. J Mol Biol. 2008 Apr 4;377(4):1216-27. doi: 10.1016/j.jmb.2008.01.082. Epub 2008 Feb 4.
Ref 75 Dicarba analogues of -conotoxin RgIA. Structure, stability, and activity at potential pain targets. J Med Chem. 2014 Dec 11;57(23):9933-44. doi: 10.1021/jm501126u. Epub 2014 Dec 1.
Ref 76 Structure-Function Elucidation of a New -Conotoxin, MilIA, from Conus milneedwardsi. Mar Drugs. 2019 Sep 16;17(9):535. doi: 10.3390/md17090535.
Ref 77 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 78 Structure-function elucidation of a new -conotoxin, Lo1a, from Conus longurionis. J Biol Chem. 2014 Apr 4;289(14):9573-83. doi: 10.1074/jbc.M114.556175. Epub 2014 Feb 24.
Ref 79 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 80 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 81 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 82 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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