Description:
<jats:title>Abstract</jats:title><jats:p>Parabutoxin 3 (PBTx3), a short‐chain α‐K<jats:sup>+</jats:sup> neurotoxin from the scorpion, <jats:italic>Parabuthus transvaalicus</jats:italic>, is a 37‐residue polypeptide cross‐linked by three disulphide bridges. The affinity towards Kv1 channels is very weak (<jats:italic>K</jats:italic>d ≈ 79 µ<jats:sc>m</jats:sc> for Kv1.1 channels), or moderate (<jats:italic>K</jats:italic>d ≈ 500 n<jats:sc>m</jats:sc> for Kv1.2 and Kv1.3 channels). In an effort to generate a more potent K<jats:sup>+</jats:sup> channel blocker, we recombinantly produced a mutant PBTx3 by the introduction of an aromatic amino acid, fenylalanine in close proximity of the crucial lysine 26 residue, to create a functional diad similar to subfamily three α‐K<jats:sup>+</jats:sup> toxins. The mutant was tested for his ability to block Kv1.1, Kv1.2 and Kv1.3 channels in <jats:italic>Xenopus laevis</jats:italic> oocytes: a hundred‐fold higher affinity towards Kv1.1 channels and a fivefold increase in affinity towards Kv1.3 channels was observed, when compared to the wild‐type toxin. The effect on Kv1.2 channels was similar to the wild‐type toxin, indicating a specific interaction site for the mutated residue onto the different Kv‐type channels.</jats:p>