8.B.12 The Spider Toxin (STx2) Family Phoneutria nigriventer toxins, PnTx2-5 and PnTx2-6, markedly delay the fast inactivation kinetics of neuronal-type sodium channels, but they have differences in their interactions with the channel (Matavel et al., 2009). PnTx2-6 has an affinity 6 times higher than that of PnTx2-5, and its effects are not reversible within 10-15 min of washing. PnTx2-6 partially (59%) competes with the scorpion alpha-toxin AaHII, but not with the scorpion beta-toxin CssIV, thus suggesting a mode of action similar to that of site 3 toxins. However, PnTx2-6 is not removed by strong depolarizing pulses, as in the known site 3 toxins. Matavel et al., 2009 also established that the cysteines in these poorly helical toxins are in their oxidized form.
This family belongs to the Huwentoxin Superfamily.
References:
Liu, Z., J. Dai, L. Dai, M. Deng, Z. Hu, W. Hu, and S. Liang. (2006). Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena. J. Biol. Chem. 281: 8628-8635.
Matavel, A., C. Fleury, L.C. Oliveira, F. Molina, M.E. de Lima, J.S. Cruz, M.N. Cordeiro, M. Richardson, C.H. Ramos, and P.S. Beirão. (2009). Structure and activity analysis of two spider toxins that alter sodium channel inactivation kinetics. Biochemistry 48: 3078-3088.
Souza, A.H., J. Ferreira, M.d.o.N. Cordeiro, L.B. Vieira, C.J. De Castro, G. Trevisan, H. Reis, I.A. Souza, M. Richardson, M.A. Prado, V.F. Prado, and M.V. Gomez. (2008). Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain 140: 115-126.
Vassilevski, A.A., M.Y. Sachkova, A.A. Ignatova, S.A. Kozlov, A.V. Feofanov, and E.V. Grishin. (2013). Spider toxins comprising disulfide-rich and linear amphipathic domains: a new class of molecules identified in the lynx spider Oxyopes takobius. FEBS J. 280: 6247-6261.
Vieira, L.B., C. Kushmerick, H.J. Reis, C.R. Diniz, M.N. Cordeiro, M.A. Prado, E. Kalapothakis, M.A. Romano-Silva, and M.V. Gomez. (2003). PnTx3-6 a spider neurotoxin inhibits K⁺-evoked increase in [Ca²⁺](i) and Ca²⁺-dependent glutamate release in synaptosomes. Neurochem Int 42: 277-282.
Vieira, L.B., C. Kushmerick, M.E. Hildebrand, E. Garcia, A. Stea, M.N. Cordeiro, M. Richardson, M.V. Gomez, and T.P. Snutch. (2005). Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6. J Pharmacol Exp Ther 314: 1370-1377.
Examples:
TC#	Name	Organismal Type	Example
8.B.12.1.1	*The spider toxin Tx2-5 (Matavel et al., 2009).*	Spiders	*Tx2-5 of Phoneutria nigriventer* (P29424)**

8.B.12.1.3	Hainantoxin XV-2, HnTx-XV-2 of 117 aas.	Spiders	HnTx-XV-2 of Haplopelma hainanum

8.B.12.1.4	Cystine knot toxin of 114 aas	Spiders	Cystine knot toxin of Dolomedes mizhoanus

8.B.12.1.5	Omega-ctenitoxin-Pn4a (CnTx-Pn4a; neurotoxin Tx3-6; α1-β toxin) of 90 aas and 1 N-terminal TMS. The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. It is a potent blocker of high voltage-activated calcium channels, acting mainly on P/Q-type (Cav2.1/CACNA1A) calcium channels and with a minor effect on L- (Cav1/CACNA1) and N-type (Cav2.2/CACNA1B) calcium channels (Vieira et al. 2005). It blocks glutamate release in synaptic transmission mediated by calcium channels (Vieira et al. 2003). The toxin also inhibits the KCl-induced increase of intrasynaptosomal free calcium (Souza et al. 2008).		*Toxin of Phoneutria nigriventer* (Brazilian armed spider)**

8.B.12.1.6	Spiderine-1a of 166 aas and 1 TMS. It has antimicrobial, insecticidal, cytolytic and cytotoxic activity, and is active against E. coli, E. faecalis, B. subtilis, A. globiformis, P. aeruginosa and S. aureus in submicromolar or low micromolar ranges. It also lyses human erythrocytes and kills HeLA and A549 cells (Vassilevski et al. 2013).		Spiderine of Oxyopes takobius (Lynx spider) (Oxyopes foliiformis)

Examples:
TC#	Name	Organismal Type	Example