CboK7, also known as α-KTx 2.24, is a toxin produced by a species of scorpion, Centruroides bonito. It blocks voltage-gated K+ channels, with most affinity for the Kv1.2 channel.
| CboK7 | |||||||
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| Identifiers | |||||||
| Symbol | ? | ||||||
| UniProt | C0HM78 | ||||||
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| Identifiers | |
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3D model (JSmol)
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| Properties | |
| C189H302N52O52S7 | |
| Molar mass | 4359.23 g·mol−1 |
| Related compounds | |
Related compounds
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CboK3, CboK4 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Etymology
editThis toxin is known by two names: CboK7 and α-KTx 2.24.[1]
The name CboK7 comes from the species the toxin was found in, Centruroides bonito. K denotes the fact that the toxin affects potassium channels. Seven of these toxins were found in these species, and this one was given the number 7.
The name α-KTx 2.24 is based on another naming system; scorpion toxins that affect potassium channels are referred to as KTx, and further classified with a Greek letter into one of the seven existing subfamilies, with this toxin belonging to the alpha family, which is characterized by a short chain and having three or four disulfide bridges.[1][2]
Chemistry
editFamily
editCentruroides bonito species is found in the Mexican state Guerrero. The Centruroides bonito has seven different peptides, CboK1 to CboK7. These seven toxins are part of the α-KTx family. The α-KTx family, also called parabutoxin, has very low pH values.[3]
Structure
editCboK7 has a sequence of 39 amino acids residues long and weighs 4,365 Da.[4]
All CboK peptides contain a functional dyad of Lys and Tyr.[1] The functional dyad refers to a pair of amino acid residues in toxins that target Kv1 channels, which plays a key role in toxin-binding. It typically consists of a lysine residue paired with a hydrophobic residue, such as tyrosine, phenylalanine or leucine.[5]
Sequence: TFINVKCTSPKQCLKPCKDLYGPHAGEKCMNGKCKCYKV[4]
Homology
editCboK7 varies from CboK3 and CboK4 by one amino acid. Specifically, CboK7 has Phe instead of Ile in CboK3 and Val instead of Pro in CboK4.[1]
Target & mode of action
editCboK7 toxin affects voltage-gated potassium channels. It is capable of completely blocking Kv1.2 type channels, with a high affinity (24pM), and can partially inhibit Kv1.1 and Kv1.3 channels, but with a much lower affinity (141nM and 20.4nM respectively).[1]
The blocking occurs by the binding of CboK7 to the potassium channel. Specifically, its lysine residue blocks the selectivity filter,[1] which is the part of the channel that is structured in a way that allows only K+ ions to pass through. Blocking this filter prevents the flow of ions through the channel.[6]
The inhibition of potassium flow through the Kv1.2 channel decreases Kv currents and increases excitability of Dorsal root ganglion neurons, which is associated with symptoms of neuropathic pain.[7]
The impact of CboK7 on humans has not yet been reported, but the typical symptoms of the Centruroides genus venom poisoning are known.[8]
Treatment and Therapeutic use
editCboK7 has shown effectiveness for inhibiting Kv1.2. Other Kv1.2 inhibitors have demonstrated efficacy in the treatment of gain-of-function mutations in KCNA2-encephalopathy patients. Some Kv1.2 channels are located in the brain, secured by the blood-brain barrier, which CboK7 might not be able to bypass.[1]
References
edit- ^ a b c d e f g Shakeel, Kashmala; et al. (15 August 2023). "Of seven new K+ channel inhibitor peptides of Centruroides bonito, α-KTx 2.24 has a picomolar affinity for Kv1.2". Toxins. 15 (8): 506. doi:10.3390/toxins15080506. PMID 37624263.
- ^ "InterPro". www.ebi.ac.uk. Retrieved 2024-10-23.
- ^ "InterPro". www.ebi.ac.uk. Retrieved 2024-10-23.
- ^ a b "UniProt". www.uniprot.org. Retrieved 2024-10-23.
- ^ Mouhat, Stephanie; De Waard, Michel; Sabatier, Jean-Marc (February 2005). "Contribution of the functional dyad of animal toxins acting on voltage-gated Kv1-type channels". Journal of Peptide Science. 11 (2): 65–68. doi:10.1002/psc.630. ISSN 1075-2617. PMID 15635666.
- ^ "Nervous system | Definition, Function, Structure, & Facts | Britannica". www.britannica.com. 2024-09-25. Retrieved 2024-10-23.
- ^ "Channelpedia - Kv1.2". channelpedia.epfl.ch. Retrieved 2024-10-23.
- ^ Shamoon, Zafar; Peterfy, Ryan J.; Hammoud, Sami; Khazaeni, Babak (2024), "Scorpion Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 28613678, retrieved 2024-10-23