Anuroctoxin
Anuroctoxin (α-KTx 6.12) is a peptide from the venom of the Mexican scorpion Anuroctonus phaiodactylus. This neurotoxin belongs to the alpha family of potassium channel acting peptides. It is a high-affinity blocker of Kv1.3 channels.[1]
Sources
[edit]Anuroctoxin is a peptide which is derived from the scorpion Anuroctonus phaiodactylus; this scorpion belongs to the scorpion family Iuridae.
Chemistry
[edit]Scorpion toxins acting on K+ channels (KTx) are grouped in three different families: the α-,β- and γ-scorpion toxins.[2] The Anuroctoxin peptide belongs to the α-KTx group,[1] which are short peptides that block potassium channels, consisting of 30 to 40 amino acids with three or four disulfide bridges.[3] Based on a phylogenetic analysis Anuroctoxin is included in subfamily six in the α-KTx phylogenetic tree; its systematic name is α-KTx 6.12.[1]
Structure
[edit]Anuroctoxin has 35 amino acids with four disulfide bridges. Its molecular weight is 4082.8 Da.[1]
Target
[edit]Patch-clamp experiments have shown that Anuroctoxin is a potent blocker of Kv1.3 (Kd= 0.73 nM) potassium channels.[1] Besides Kv1.3/KCNA3 channels, Anuroctoxin also significantly inhibits Kv1.2 (Kd = 6 nM) potassium channels.[1] Anuroctoxin does not block any of the following channels: calcium-activated KCa3.1/KCNN4 potassium channels, Shaker IR, Kv1.1/KCNA1, and Kv2.1/KCNB1 potassium channels.[1]
Mode of action
[edit]The α-KTx inhibition of the potassium channels is mediated by a simple bimolecular plugging mechanism: the extracellular pore, which has a specific receptor site, is occluded by a single toxin molecule binding to it.[2] Whether this block is voltage dependent, which is common in scorpion toxins[2] remains to be seen. This pore block is however fully reversible, which implies that it is not a potent neurotoxin.[1]
References
[edit]- ^ a b c d e f g h Bagdany, M.; C. V. Batista; et al. (2005). "Anuroctoxin, a new scorpion toxin of the alpha-KTx 6 subfamily, is highly selective for Kv1.3 over IKCa1 ion channels of human T lymphocytes". Mol Pharmacol. 67 (4): 1034–1044. doi:10.1124/mol.104.007187. PMID 15615696. S2CID 12308227.
- ^ a b c Tytgat, J.; Chandy, K. G.; Garcia, M. L.; Gutman, G. A.; Martin-Eauclaire, M. F.; van der Walt, J. J.; Possani, L. D. (1999). "A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies". Trends Pharmacol Sci. 20 (11): 444–7. doi:10.1016/S0165-6147(99)01398-X. PMID 10542442.
- ^ Tytgat J, Debont T, Rostoll K, Müller GJ, Verdonck F, Daenens P, van der Walt JJ, Possani LD (1998). "Purification and partial characterization of a 'short' insectotoxin-like peptide from the venom of the scorpion Parabuthus schlechteri". FEBS Lett. 441 (3): 387–91. doi:10.1016/s0014-5793(98)01589-0. PMID 9891977.
