Biochemistry
BmTx3 consists of an α-helix and two β-sheet segments cross-linked by three disulfide bridges (Cs-α/β motif). [1] It is a short chain peptide with a molecular mass of 3751.6 Da; it consists of 37 amino acids. [1]
BmTx3 is a neurotoxin, which is a component of the venom of the scorpion Buthus Martensi Karsch. It blocks A-type potassium channels in the central nervous system and hERG-channels in the heart.
BmTx3 was originally purified from the venom of the Chinese scorpion, Buthus Martensi Karsch. BmTx3 is a “short-chain” peptide like other potassium channel blockers in the scorpion venom and added to the phylogenetic tree in the subfamily α-KTx15. Its 3D structure has not yet been elucidated, but based on sequence similarity it likely resembles the 3D structure of BmTx1 [1] or Discrepin. [2]
BmTx3 consists of an α-helix and two β-sheet segments cross-linked by three disulfide bridges (Cs-α/β motif). [1] It is a short chain peptide with a molecular mass of 3751.6 Da; it consists of 37 amino acids. [1]
BmTx3 is the first toxin from the scorpion α-KTx subfamily 15 [3] with two functional faces. As all α-KTx peptides, BmTx3 blocks A-type (IA) potassium currents (KD = 54 nM). BmTx3 blocks primarily the Kv4.x proteins and has a higher affinity for Kv4.1 channels than for Kv4.2 and Kv4.3 channels. [4] The second functional face of BmTx3 blocks the hERG (human Ether-à-go-go) channel (KD = 2 μM), a characteristic belonging to γ-KTx peptides. [4] BmTx3 binding site seems essentially localized in neurons but could also be present in glial cells, endothelial cells and/or arterial smooth muscle cells. The distribution of BmTx3 binding sites is heterogeneous; a high density is found in the caudate–putamen and accumbens nucleus, thalamus, hippocampal formation and cerebellum. [4]
The functional face of “short-chain” scorpion toxins is built of two important dyads (Lys and Tyr) on the β-sheet side. Lysine plugs deep into the channel pore and Tyrosine, as penultimate or ultimate and hydrophobic residue, turns it to fixate it, leading to a physical occlusion of the channel pore. [1] This is supported by the finding that deletion of the two C-terminal residues (sBmTx3-delYP) results in loss of ability to block IA-current. [1]
The other functional face is thought to be situated at the α-helix-side and composed of Arg18 and Lys19, like the functional face of other hERG toxins. It is known that α-KTx peptides use the β-sheet side to interact with the receptor, whereas γ-KTx peptides usually use their α-helix-side. [5] As BmTx3 seems to use both sides to bind to different potassium channels, it might be an evolutionary transient between the two families. [5]
When injected into mice it causes epileptiform behavior. [6] This might be due to its effect on A-type K+ channels, which, like the Kv4.x, are involved in action potential back propagation, firing frequency, spike initiation and action potential waveform determination. [4] Blocking of the hERG channel can cause drug-induced long QT syndrome, arrhythmias and ventricular fibrillation which can result in death. [5]
Slotoxin is a peptide from Centruroides noxius Hoffmann scorpion venom. It belongs to the short scorpion toxin superfamily.
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.
In molecular biology, the BmKK2 toxins are a family of scorpion toxins. They belong to the scorpion toxin subfamily alpha-KTx 14. They include a novel short-chain peptide from the Asian scorpion Mesobuthus martensii Karsch, a potassium channel blocker composed of 31 amino acid residues. The peptide adopts a classical alpha/beta-scaffold for alpha-KTxs. BmKK2 selectively inhibits the delayed rectifier K+ current, but does not affect the fast transient K+ current.
BeKm-1 is a toxin from the Central Asian scorpion Buthus eupeus. BeKm-1 acts by selectively inhibiting the human Ether-à-go-go Related Gene (hERG) channels, which are voltage gated potassium ion channels.
Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium 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.
AmmTX3, produced by Androctonus mauretanicus, is a scorpion toxin of the α-KTX15 subfamily. The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current through this channel.
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.
Spinoxin is a 34-residue peptide neurotoxin isolated from the venom of the Malaysian black scorpion Heterometrus spinifer. It is part of the α-KTx6 subfamily and exerts its effects by inhibiting voltage-gated potassium channels, specifically Kv1.2 and Kv1.3.
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.
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.
BmP02, also known as α-KTx 9.1 or Bmkk(6), is a toxin from the Buthus Martensi Karsch (BmK) scorpion. The toxin acts on potassium channels, blocking Kv1.3 and slowing the deactivation of Kv4.2. BmP02 is not toxic to humans or mice.
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).
BmK NSPK is a toxin isolated from the venom of the Chinese armor-tail scorpion, which specifically targets voltage gated potassium channels (Kv), resulting in a direct inhibition of outward potassium current.
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).
BmKTX is a scorpion neurotoxin which blocks the voltage gated potassium channel Kv1.3.
