Chemistry: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-KTx.[2] KTx is the abbreviation of kaliotoxin, which is a potassium channel toxin.[2] There are three KTx families: α-, β- and γ-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-KTx family because it is a short-chain toxin in the venom of a scorpion.[2] Furthermore, the α-KTx family is divided in subfamilies, classified by the alignment of cysteine.[2] A nomenclature α-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-KTx 24.1, being the first member in the 24th subfamily of α-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 (Kd) 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 Kd of 92 nM and hKv1.3 with a Kd 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 Kv channel blocker toxins.[1]
Toxicity
The venom of Pandinus imperator is not lethal to humans.[1]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 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).
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