Hg1 (toxin)
Hg1 is a Kunitz-type peptide ion channel toxin derived from the scorpion Hadrurus gertschi. Its mode of action is that it selectively inhibits the potassium channel Kv1.3 and, with a lower affinity, channels Kv1.1 and Kv1.2.
Etymology and source
The Hg1 toxin is named after the Mexican scorpion Hadrurus gertschi that produces it, which belongs to the Caraboctonidae family. This scorpion is also known as Hoffmannihadrurus gertschi. The alternative name of Hg1 is Delta-Ktx 1.1.Chemistry
Hg1 has a sequence of 88 amino acids with three disulfide bonds between Cys29-Cys79, Cys38-Cys62 and Cys54-Cys75. Hg1 has a molecular weight of 9,855 Da. It belongs to the Kunitz-type potassium channel family toxins. These toxins are classified in three different groups, according to their disulfide bridge pattern. Hg1 is classified as a member of the first group, showing classical disulfide pairing, comparable to the HWTX-XI toxin in spiders, dendrotoxin K in snakes, and APEKTx1 in sea anemones.Amino acid sequence
The amino acid sequence of Hg1 is:Target
The toxin primarily inhibits voltage-gated potassium channels and is highly selective for channel Kv1.3 with an IC50 of 6.2 ± 1.2 nM. With a lower affinity the toxin also inhibits potassium channels Kv1.1 and Kv1.2.| Channel | Reduction in ion channel conductance |
| Kv1.1 | <50% |
| Kv1.2 | <50% |
| Kv1.3 | ≈80% |
Similar to other Kunitz-type toxins, recombinant Hg1 was revealed to inhibit the serine protease trypsin, having the highest affinity to it compared to other Kunitz-type potassium channel toxins, such as LmKTT-1a, LmKTT-1b, LmKTT-1c, and BmKTT-1.