| Pandinotoxin | |
|---|---|
 Schematic diagram of the three-dimensional of Pandinotoxin | |
| Identifiers | |
| Organism | |
| Symbol | N/A |
Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator . They are selective blockers of voltage-gated potassium channels [1]
The source for the pandinotoxins is the venom of the scorpion Pandinus imperator . [1]
The toxins of the family are designated pandinotoxin (PiTX)-Kα, PiTX-Kβ, and PiTX-Kγ [2] They are members of the α-KTx family of scorpion toxins. [1]
| The sequences of Pandinotoxins |
|---|
CTX
PiTXK- α
PiTXK- β
PiTX-K γ
Figure 1: Sequence of Pandinotoxins. Adapted from Solution Structure for Pandinus Toxin K-R (PiTX-KR) [1] |
The amino acid sequences of PiTX-K α and PiTX-K β are identical, except for the seventh amino acid: a proline in PiTX-Kα and a glutamic acid in PiTX-Kβ [2] (see Fig.1).
PiTX-Kα and PiTX-Kβ are 35-residue peptides, which are found to have an α-helix from residues 10 to 21 and two β-sheets (β 1 is from residues 26-28, β 2 is from residues 33-35). One face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). [1] PiTX-K α and PiTX-K β have only two β-sheets whereas other members of the family have three additional amino acid residues at the N-terminal portion, which forms a third β-sheet. [1]
Pandinotoxin Kγ has not yet been investigated.
Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type voltage-gated potassium channels. [3] They also block the delayed rectifier, slowly inactivating channels of the subfamily A member 2 (Kv1.2/KCNA2) [1] and they can reversibly block the shaker B potassium-channels (Kv1.1 sub-family). [4]
The residue K27, a lysine at place 27 of the protein sequence, interacts with the voltage sensitivity blocking activity of CTX channels. It is conserved among PiTX-K α and PiTX-K β. This amino acid is located nearby the selectivity filter of the pore [5] and it is responsible for the interaction with A-type channels by being inserted in the pore of the ion channels. [1] The structural differences in the backbone and side chain between PiTX-Kα and CTX result in a higher affinity for A-type channels for PiTX-Kα. [1] The affinity for the Shaker B K+ channel is significantly smaller for PiTX-Kβ in comparison with PiTX-Kα owing to the changes in the seventh residue. [4]
Intraplantarly injection of PiTX-Kα before or after the administration of diclofenac produces a significant reduction in spontaneous flinching, mechanical allodynia and thermal hyperalgesia in a rat model for bone cancer. Downregulation of PiTX-Kα almost completely eliminates diclofenac-induced anti-nociception. [6]
Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker) that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. It is named after Charybdis, a sea monster from Greek myth.
The emperor scorpion, Pandinus imperator, is a species of scorpion native to rainforests and savannas in West Africa. It is one of the largest scorpions in the world and lives for 6–8 years. Its body is black, but like other scorpions it glows pastel green or blue under ultraviolet light. It is a popular species in the pet trade, and is protected by CITES to prevent over-collecting that might impact the species' survival.
Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.
Slotoxin is a peptide from Centruroides noxius Hoffmann scorpion venom. It belongs to the short scorpion toxin superfamily.
Agitoxin is a toxin found in the venom of the scorpion Leiurus quinquestriatus hebraeus. Other toxins found in this species include charybdotoxin (CTX). CTX is a close homologue of Agitoxin.
Imperatoxin I (IpTx) is a peptide toxin derived from the venom of the African scorpion Pandinus imperator.
Cobatoxin is a toxin present in the venom of the scorpion Centruroides noxius. It blocks two potassium channel subtypes; voltage-gated and calcium-activated channels.
Discrepin (α-KTx15.6) is a peptide from the venom of the Venezuelan scorpion Tityus discrepans. It acts as a neurotoxin by irreversibly blocking A-type voltage-dependent K+-channels.
Butantoxin (BuTX) is a compound of the venom of three Brazilian and an Argentinean scorpion species of the genus Tityus. Butantoxin reversibly blocks the voltage-gated K+ channels Shaker B and Kv1.2, and the Ca2+-activated K+ channelsKCa 1.1 and KCa 3.1.
Pi3 toxin is a purified peptide derivative of the Pandinus imperator scorpion venom. It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, Pi2.
Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.
HsTx1 is a toxin from the venom of the scorpion Heterometrus spinifer. HsTx1 is a very potent inhibitor of the rat Kv1.3 voltage-gated potassium channel.
HgeTx1 (systematic name: α-KTx 6.14) 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.
Pi4 is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels.
Limbatustoxin, is an ion channel toxin from the venom of the Centruroides limbatus scorpion. This toxin is a selective blocker of BK channels, calcium-activated potassium channels.
AaTX1 is a scorpion toxin of the α-KTx15 subfamily originally found in the venom of Androctonus australis. The toxin acts as a specific blocker on Kv4.3 voltage-gated potassium channel, thereby abolishing the A-type potassium currents.
ImKTx88 is a selective inhibitor of the Kv1 ion channel family that can be isolated from the venom of the Isometrus maculatus. This peptide belongs to the α-KTx subfamily and is classified as a pore-blocking toxin.
Pi5 toxin is a peptide found in the venom of the African emperor scorpion Pandinus imperator. Pi5 inhibits human Kv1.2 and Kv1.3 channels as well as Drosophila Shaker B potassium channels.
OdK2 is a toxin found in the venom of the Iranian scorpion Odonthobuthus doriae. It belongs to the α-KTx family, and selectively blocks the voltage-gated potassium channel Kv1.3 (KCNA3).
OSK3, from the venom of the scorpion Orthochirus scrobiculosus, is a potassium channel blocker that belongs to the α-KTx8 subfamily and targets the voltage-gated potassium channels KCNA2 (Kv1.2), and KCNA3 (Kv1.3).
