Pi5

Pi5 toxin is a peptide found in the venom of the African emperor scorpion Pandinus imperator. Pi5 inhibits human Kv1.2 and Kv1.3 channels as well as Drosophila Shaker B potassium channels.

Etymology and source

Pi5 is a peptide that is purified from the venom of the African scorpion Pandinus imperator.^[1] Pi in Pi5 is short for the 5th identified peptide of the scorpion Pandinus imperator.^[1] As of July 2017, a total of 7 peptides purified from the venom of this scorpion have been characterized (Pi1-7).^[1]

Chemistry

Pi5 is part of the toxin family αあるふぁ-KTx.^[2] KTx is the abbreviation of kaliotoxin, which is a potassium channel toxin.^[2] There are three KTx families: αあるふぁ-, βべーた- and γがんま-KTx.^[2] The classification of toxins into these families is based on the size of the peptides, their chronological appearance, toxicity to humans, and ion-channel specificity.^[2] Pi5 belongs to the αあるふぁ-KTx family because it is a short-chain toxin in the venom of a scorpion.^[2] Furthermore, the αあるふぁ-KTx family is divided in subfamilies, classified by the alignment of cysteine.^[2] A nomenclature αあるふぁ-KTx m.n. in which m represents the subfamily and n represents the member of that subfamily has been proposed.^[3] Pi5 has been given the systematic name of αあるふぁ-KTx 24.1, being the first member in the 24th subfamily of αあるふぁ-KTx toxins.^[1]

The Pi5 peptide has a molecular weight of 3334.00 Da. and contains 33 amino acids.^[1] Eight of the amino acids are cysteines, and they form a total of four disulfide bonds.^[1] The amino acid sequence of Pi5 is: VAKCSTSECGHACQQAGCRNSGCRYGSCICVGC.^[1]

Target

Pi5 blocks Drosophila Shaker B K+ channels as well as human Kv1.2 and Kv1.3 channels.^[1]

Drosophila Shaker B K+ channels

Pi5 blocks Drosophila Shaker B K⁺ channels with low affinity.^[1] The inhibition of these Shaker B K⁺ channels is reversible.^[1] The dissociation constant (K_d) of the inhibition is 540 nM.^[1]

hKv1.2 and hKv 1.3 channels

Pi5 inhibits the human voltage-dependent potassium channels Kv1.2 and Kv1.3.^[1] These channels are coded respectively by the genes KCNA2 and KCNA3 and their inhibition is reversible.^[1] hKv1.2 is inhibited with a K_d of 92 nM and hKv1.3 with a K_d of 77 nM.^[1]

Mode of action

The Pi5 toxin scales down the ion currents through ion channels. The kinetics of the channels remain unaltered. Furthermore, the blockage of the channels is not voltage-dependent, which is often found with K_v channel blocker toxins.^[1]

Toxicity

The venom of Pandinus imperator is not lethal to humans.^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p Olamendi-Portugal T, Csoti A, Jimenez-Vargas JM, Gomez-Lagunas F, Panyi G, Possani LD. Pi5 and Pi6, two undescribed peptides from the venom of the scorpion Pandinus imperator and their effects on K(+)-channels. Toxicon 2017 Jul;133:136-144.
^ ^a ^b ^c ^d ^e ^f Tytgat J, Chandy KG, Garcia ML, Gutman GA, Martin-Eauclaire MF, van der Walt JJ, et al. A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies. Trends Pharmacol Sci 1999 Nov;20(11):444-447.
^ Miller C. The charybdotoxin family of K+ channel-blocking peptides. Neuron 1995;15(1-5).

[Olamendi-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p Olamendi-Portugal T, Csoti A, Jimenez-Vargas JM, Gomez-Lagunas F, Panyi G, Possani LD. Pi5 and Pi6, two undescribed peptides from the venom of the scorpion Pandinus imperator and their effects on K(+)-channels. Toxicon 2017 Jul;133:136-144.

[Tytgat-2] ^ ^a ^b ^c ^d ^e ^f Tytgat J, Chandy KG, Garcia ML, Gutman GA, Martin-Eauclaire MF, van der Walt JJ, et al. A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies. Trends Pharmacol Sci 1999 Nov;20(11):444-447.

[3] Miller C. The charybdotoxin family of K+ channel-blocking peptides. Neuron 1995;15(1-5).

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