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Anuroctoxin

For years there were only neurotoxins discovered which acted on either the sodium channels or the calcium channels. This changed in 1982 when it was discovered that a peptide in the venom of the scorpion Centruroides noxius inhibited potassium currents. These discoveries of potassium channel inhibiting neurotoxins kept coming. One of them is the Anuroctoxin which is a peptide that is derived from the venom of the Mexican scorpion Anuroctonus phaiodactylus. This neurotoxin belongs to the alpha family of potassium channel acting peptides. It blocks especially the Kv1.3/KCNA3 channels, which it has a high affinity for.

Source
Anuroctoxin is a peptide which is derived from the scorpion Anuroctonus phaiodactylus, this scorpion belongs to the Iuridae family of scorpions.

Chemistry
The K+ channel acting peptides are grouped in three different families: the α-,β- and γ-scorpion toxins. These are collectively called the KTx’s ( K+ channel toxins). The Anuroctoxin peptide belongs to the α-KTx group , these are short peptides which block potassium channels and consist of 30 to 40 amino acids with three or four disulfide bridges. With use of phylogenetics it was analyzed in which subfamily of the α-KTx family the Anuroctoxin belongs too. This analyses showed that Anuroctoxin is included in subfamily six in the α-KTx phylogenetic tree, its systematic name is 6.12.

Structure
A 3D model of the Anuroctoxin, which was obtained with homology modeling and and molecular dynamics, showed that the Anuroctoxin is a peptide with 35 amino acid components with four disulfide bridges. The molecular weight of the Anuroctoxin was obtained with use of electrospray ionization which showed that this Anuroctoxin peptide has a molecular weight of 4082.8 Da.

Target
Patch-clamp experiments have shown that Anuroctoxin is a potent blocker of Kv1.3/KCNA3 (Kd= 0.73 nM) channels. Besides Kv1.3/KCNA3 channels, Anuroctoxin also significantly inhibit Kv1.2/KCNA2 (Kd= 6 nM) channels with an approximately 7-fold lower affinity than Kv1.3/KCNA3 channels. These same experiments showed that 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.

Mode of action
The α-KTx inhibition of the potassium channels is mediated by a simple bimolecular plugging mechanism: the extra cellular pore, which has a specific receptor site, is occluded by the α-KTx binding to it. But whether this block is voltage dependent, which is common in scorpion toxins remains to be seen. This pore block is however fully reversible, which implies that it is not a potent neurotoxin. And the dose–response relationship of the Anuroctoxin on the inhibition of the Kv1.3 channel showed a Hill coefficient of approximately one; which suggest that one peptide interacts with one potassium pore. .