HgeTx1
HgeTx1 is a toxin produced by the Mexican scorpion Hoffmanihadrurus gertschi that is a reversible blocker of the Shaker B K+-channel, a type of voltage-gated potassium channels.
All α-KTx category toxins are peptides that contain between 20 and 40 amino acids and contain three or four disulfide bridges. HgeTx1 consists of 36 amino acids and has four disulfide bridges. These disulfide bridges exist between Cys1–Cys5, Cys2–Cys6, Cys3–Cys7 and Cys4–Cys8. It has a molecular mass of 3950 atomic mass units.
Target
Electrophysiological experiments have been performed to investigate the physiological effect of HgeTx1 on Shaker B K+-channels in insect cell cultures. These recordings show that HgeTx1 reversibly blocks the Shaker B K+-channel. This blockage follows a Michaelis-Menten saturation relationship with a Kd of 52 nM. However, there is no report of selectivity for or blockage of other subtypes of K+-channels.
Mode of action
HgeTx1 has only been investigated for its effectiveness on the Shaker B K+-channel, where the toxin seems to work as a plug that blocks the pore's ion conductance. This blockage follows the functional dyad model that underlies most α-KTx toxins. In the functional dyad model, a lysine residue interacts with a hydrophobic Leu, Tyr, Met or Phe residue, in order to recognize the K+-channel. On the extracellular side of the channel, the side-chain of the lysine residue will enter the pore and subsequently block the channel. In HgeTx1, it seems likely that the Lys24 residue will interact with the hydrophobic Met33 or Leu34 residue according to the functional dyad model, which allows it to block the Shaker B K+-channel.
Toxicity
Scorpions of the family Caraboctonidae, each of which produce a cocktail of different toxins, are not considered dangerous to humans.