Kurtoxin

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Kurtoxin is a toxin found in the venom of the South African scorpion Parabuthus transvaalicus . It affects the gating of voltage-gated sodium channels and calcium channels. [1]

Contents

Sources

Many venoms are evolved among animals and most of them is a peptide in nature. [2] Kurtotoxin is found in the venom of the South African scorpion Parabuthus transvaalicus.

Chemistry

Kurtoxin is a protein containing 63 amino acid residues with a mass of 7386.1 daltons. Its formula is C324H478N94O90S8. It can be isolated from the venom of Parabuthus transvaalicus by high-performance liquid chromatography (HPLC). Kurtoxin is closely related to α-scorpion toxins, a family of toxins that slow inactivation of voltage-gated sodium channels. The complete primary amino-acid sequence of kurtoxin is: KIDGYPVDYW NCKRICWYNN KYCNDLCKGL KADSGYCWGW TLSCYCQGLP DNARIKRSGR CRA.

Target

In research on Xenopus oocytes it was found that kurtoxin affects low-threshold α1G and α1H calcium channels, but not the high-threshold α1A, α1B, α1C, and α1E Ca channels. Like other α-scorpion toxins kurtoxin was also found to interact with voltage-gated sodium channels. In rat neurons, less selectivity for kurtoxin on calcium channels is found. Here the toxin interacts with high affinity with T-type, L-type, N-type, and P-type channels.

Mode of action

Kurtoxin inhibits ion calcium channels by modifying channel gating. The effect of the toxin is voltage-dependent. In a voltage-clamp experiment it was found that calcium channels are more strongly inhibited by minor depolarization than by a strong depolarization of the cell. The peptide toxin binds close to the channel voltage sensor and thereby produces complex gating modifications specific for each channel type. In rats, kurtoxin inhibited T-type, L-type, and N-type Ca channels and facilitated P-type channels. Deactivation was accelerated in T-type and L-type channels, slowed down in P-type channels and not affected in N-type calcium channels. Kurtoxin also has an effect on sodium channels. It slows down both activation and inactivation of the channel.

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References

  1. ↑ Won Lee, Chul (February 13, 2012). "Solution Structure of Kurtoxin: A Gating Modifier Selective for Cav3 Voltage-Gated Ca2+ Channels". Biochemistry. 51 (9). American Chemical Society: 1862–1873. doi:10.1021/bi201633j . Retrieved 20 December 2024.
  2. ↑ Pennington, Michael W.; Czerwinski, Andrzej; Norton, Raymond S. (1 June 2018). "Peptide therapeutics from venom: Current status and potential". Bioorganic & Medicinal Chemistry. 26 (10). Elsevier: 2738–2758. doi:10.1016/j.bmc.2017.09.029. PMID   28988749 . Retrieved 21 December 2024.
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