kurtoxin
{{Short description|Toxin found in scorpion venom}}
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. {{cite journal |last1=Won Lee |first1=Chul |title=Solution Structure of Kurtoxin: A Gating Modifier Selective for Cav3 Voltage-Gated Ca2+ Channels |journal=Biochemistry |date=February 13, 2012 |volume=51 |issue=9 |pages=1862–1873 |url=https://pubs.acs.org/doi/10.1021/bi201633j |access-date=20 December 2024 |publisher=American Chemical Society |doi=10.1021/bi201633j |language=English|pmc=3295331 }}
Sources
Many venoms are evolved among animals, and most of them are a peptide in nature.{{cite journal |last1=Pennington |first1=Michael W. |last2=Czerwinski |first2=Andrzej |last3=Norton |first3=Raymond S. |title=Peptide therapeutics from venom: Current status and potential |journal=Bioorganic & Medicinal Chemistry |date=1 June 2018 |volume=26 |issue=10 |pages=2738–2758 |doi=10.1016/j.bmc.2017.09.029 |url=https://www.sciencedirect.com/science/article/pii/S096808961731653X |access-date=21 December 2024 |publisher=Elsevier |pmid=28988749 |language=English}} 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.
References
{{Reflist}}
- Chuang, R.S., Jaffe, H., Cribbs, L., Perez-Reyes, E., Swartz, K.J. (1998). Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nature Neuroscience 1(8), 668–674. [http://www.jneurosci.org/cgi/reprint/22/6/2023]
- Sidach, S.S., Mintz, I.M. (2002). Kurtoxin, a gating modifier of neuronal high- and low threshold Ca channels. The Journal of Neuroscience, 22(6), 2023–2034. [http://jpet.aspetjournals.org/cgi/reprint/314/3/1370]