2mj0

Structural highlights

Function

3NO2_NAJKA Neurotoxin that irreversibly inhibits nicotinic acetylcholine receptors (nAChR) and allosterically interacts with muscarinic acetylcholine receptors (mAChR) (PubMed:11279130, PubMed:19682302). The loop II is involved in the interaction of this toxin with nAChR and mAChR (PubMed:27343701, PubMed:26242733). On nAChR, it acts as a competitive antagonist (muscle-type and alpha-7/CHRNA7) with IC(50) values in the micromolar range (PubMed:11279130, PubMed:27343701). On mAChR, in presence of ACh, it partially inhibits the effect of acetylcholine (ACh) (allosteric antagonist), whereas in the absence of ACh, it activates the receptor (allosteric agonist) (PubMed:19682302). It also shows a very weak inhibition of GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1 and GABRB3 and GABRG2) subunits (10 uM inhibit 31% current) (PubMed:26221036). In vivo, is nonlethal to mice at concentrations up to 20 mg/kg, but exerts a myorelaxant effect, induces a dose-dependent decrease in blood pressure and an increase in heart rate in mice and rats (PubMed:15581687, PubMed:17371532).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Utkin YN, Kukhtina VV, Kryukova EV, Chiodini F, Bertrand D, Methfessel C, Tsetlin VI. "Weak toxin" from Naja kaouthia is a nontoxic antagonist of alpha 7 and muscle-type nicotinic acetylcholine receptors. J Biol Chem. 2001 May 11;276(19):15810-5. Epub 2001 Feb 15. PMID:11279130 doi:http://dx.doi.org/10.1074/jbc.M100788200
2. ↑ Ogay AY, Rzhevsky DI, Murashev AN, Tsetlin VI, Utkin YN. Weak neurotoxin from Naja kaouthia cobra venom affects haemodynamic regulation by acting on acetylcholine receptors. Toxicon. 2005 Jan;45(1):93-9. PMID:15581687 doi:http://dx.doi.org/10.1016/j.toxicon.2004.09.014
3. ↑ Mordvintsev DY, Rodionov DI, Makarova MV, Kamensky AA, Levitskaya NG, Ogay AY, Rzhevsky DI, Murashev AN, Tsetlin VI, Utkin YN. Behavioural effects in mice and intoxication symptomatology of weak neurotoxin from cobra Naja kaouthia. Basic Clin Pharmacol Toxicol. 2007 Apr;100(4):273-8. PMID:17371532 doi:http://dx.doi.org/10.1111/j.1742-7843.2007.00045.x
4. ↑ Mordvintsev DY, Polyak YL, Rodionov DI, Jakubik J, Dolezal V, Karlsson E, Tsetlin VI, Utkin YN. Weak toxin WTX from Naja kaouthia cobra venom interacts with both nicotinic and muscarinic acetylcholine receptors. FEBS J. 2009 Sep;276(18):5065-75. doi: 10.1111/j.1742-4658.2009.07203.x. Epub, 2009 Aug 4. PMID:19682302 doi:http://dx.doi.org/10.1111/j.1742-4658.2009.07203.x
5. ↑ Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN. Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. PMID:26221036 doi:10.1074/jbc.M115.648824
6. ↑ Lyukmanova EN, Shulepko MA, Shenkarev ZO, Kasheverov IE, Chugunov AO, Kulbatskii DS, Myshkin MY, Utkin YN, Efremov RG, Tsetlin VI, Arseniev AS, Kirpichnikov MP, Dolgikh DA. Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors. Toxicon. 2016 Sep 1;119:274-9. PMID:27343701 doi:10.1016/j.toxicon.2016.06.012