Parabutoxin
From Wikipedia, the free encyclopedia
Parabutoxin (PBTx) is a Shaker-related voltage-gated K+ channel (Kvα1) inhibitor purified from different Parabuthus scorpion species found in southern Africa. It occurs in different forms: parabutoxin 1 (PBTx1), parabutoxin 2 (PBTx2), parabutoxin 3 (PBTx3) and parabutoxin (PBTx10). The different variants have different affinities towards Kvα1 channels.
Four different acidic peptides (PBTx1, PBTx2, PBTx3 and PBTx10) have been isolated and cloned from the venoms of three different Parabuthus scorpion species found in southern Africa. PBTx1 and PBTx3 were extracted from the venom of P. transvaalicus, PBTx2 from P. villosus and PBTx10 has been purified from P. granulatus.[1]
Chemistry
Scorpion toxins that target potassium channels have been classified into three K+ Toxin (KT) subfamilies α-KTx, β-KTx, and γ-KTx peptides. The α-KTx subfamilies are the best-studied toxins and are usually small basic “short chain toxins”. PBTx1, PBTx2 and PBTx10 structurally belong to an unusually acidic α-KTx short chain scorpion toxins subfamily and are classified as KTx11, α-KTx11.1 (PBTx1), α-KTx11.2 (PBTx2) and α-KTx11.3 (PBTx10).[1]
PBTx1, PBTx2 and PBTx10 toxins have extremely low pI values of 3.82 (PBTx1 and PBTx2) and 3.88 (PBTx10). The toxins are 36-37 amino acids in length and have six aligned cysteine residues. Usually, binding sites of Kvα1-blocking toxins (Kv1.1, Kv1.2, Kv1.3) include a lysine and a hydrophobic residue, but PBTx1, PBTx2 and PBTx10 lack the crucial pore-plugging lysine and have either Val (PBTx1, PBTx2) or Ala (PBTx10) as a substitute.[1]
PBTx3 is the tenth member of subfamily 1 (α-KTx1.10) of K+ channel-blocking peptides. The framework of PBTx3 is homologous to most other α-KTx scorpion toxins. PBTx3 has a mass of 4274 Da and consists of 37 amino acid residues with a well-conserved three-dimensional structure, stabilized by three disulphide bridges.[2][3]