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

Etymology & Source
Pi5 is a peptide that is purified from the venom of the African scorpion species Pandinus imperator (1). Pi in Pi5 is the abbreviation of Pandinus imperator (1). The 5 stands for the 5th identified peptide at that time (1). As of July 2017, a total of 7 peptides were identified in the venom of this scorpion (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). Miller proposed the nomenclature α-KTx m.n. in which m represents the subfamily and n represents the member of that subfamily (3). The alternative name of Pi5 is α-KTx 24.1, which means that Pi5 is the first member in the 24th subfamily of α-KTx (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 which form 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 hKv1.2 and hKv1.3 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 Kd of the inhibition is 540 nM (1).

hKv1.2 and hKv 1.3 channels
Pi5 inhibits the following human voltage-dependent potassium channels: hKv1.2 and hKv1.3 (1). These channels are coded by KCNA2 and KCNA3 respectively 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. Both hKv1.2 and hKv1.3 are inhibited significantly (1).

Mode of action
The Pi5 toxin scales down the currents through ion channels (1). 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.

Toxicity
The venom of the Pandinus imperator is not lethal to humans (1).

Therapeutic use
Pi5 blocks Kv1.2 and Kv1.3 with relatively low affinity (1). Therefore, it is unlikely that Pi5 toxin can be used therapeutically.