Birtoxin is a neurotoxin from the venom of theSouth African Spitting scorpion (Parabuthus transvaalicus). By changingsodium channel activation, the toxin promotes spontaneous and repetitive firing much likepyrethroid insecticides do
South African spitting scorpion(Parabuthus transvaalicus)
Birtoxin was isolated from the venom of the South African Spitting scorpion.[1] It is apeptide that is moderately toxic but very abundant in the venom.[1] Other peptide toxins found in the venom include:dortoxin, a lethal peptide;bestoxin, which causes writhing in mice; andaltitoxin, a highly depressant peptide.[2]
Generally, peptide neurotoxins can be divided into two major families, the ‘long chain neurotoxins’ (LCN) with 60- to 70-residue range and known to contain eightcysteine residues; and the ‘short chain neurotoxins’ (SCN) with 30 to 40 peptides with six or eight cysteine residues. Birtoxin, together with other birtoxin-like peptides includingbestoxin, is 58 amino-acid residues long, close to the ‘long chain’ family but with six cysteine residues. Birtoxin is reticulated by threedisulfide bridges, instead of four, compared to other LCNs.[3] Therefore, it is considered to be the evolutionary link between ‘long chain’- and ‘short chain’- families.[4][5][6][7]
Birtoxin affects thegating mechanism of sodium channels by binding to neurotoxin receptor site 4 of the channel, resulting in the lowering of the voltage threshold of the channel and a reduction in the current amplitude. Due to the change in the activation the sodium channel will open at smaller depolarisations. This causes increased excitability, which leads to symptoms such as convulsions, continuous urination, tremors and tachypnea (faster breathing).[1][8]
Birtoxin only affects mammals. No effect is found on reptiles, insects or fish. In experiments performed on mice, symptoms such as convulsions, continuous urination, tremors andtachypnea occurred 10 minutes after injection and increased during 30 minutes. An injection of 1 μg of birtoxin resulted in severeneurotoxic effects for 24 hours, but this dose is not lethal to mice. LD99 in mice is achieved at 2 μg.[1]
Anantibody against theN-terminus of the birtoxin protein structure has been shown to neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treatenvenomation.[9]
^Inceoglu, B; J Lango; I Pessah; B Hammock (2005). "Three structurally related, highly potent, peptides from the venom of possess divergent biological activity".Toxicon.45 (6):727–733.doi:10.1016/j.toxicon.2005.01.020.ISSN0041-0101.PMID15804521.
^Martin-Eauclaire, M-F; Cearda, B.; Bosmans, F.; Rossoa, J-P.; Tytgat, J.; Bougisa, P.E. (1999). "New "Birtoxin analogs" fromAndroctonus australis venom".Biochemical and Biophysical Research Communications.333 (2):524–530.doi:10.1016/j.bbrc.2005.05.148.PMID15963953.
^Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Primary and NMR three-dimensional structure determination of a novel crustacean toxin from the venom of the scorpion Centruroides limpidus limpidus Karsch".Biochemistry.33 (37):11135–11149.doi:10.1021/bi00203a010.PMID7727365.
^Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Purification and primary structure of low molecular mass peptides from scorpion (Buthus sindicus) venom".Comparative Biochemistry and Physiology A.121 (4):323–332.doi:10.1016/S1095-6433(98)10140-X.PMID10048185.
^Gordon, D.; Savarin, P.; Gurevitz, M.; Zinn-Justin, S. (1998). "Functional anatomy of scorpion toxins affecting sodium channels".Toxin Reviews.17 (2):131–159.doi:10.3109/15569549809009247.
^Cestèle, S.; Catterall, W.A. (2000). "Molecular mechanisms of neurotoxin action on voltage-gated sodium channels".Biochimie.82 (9–10):883–892.doi:10.1016/S0300-9084(00)01174-3.PMID11086218.
^Inceoglu, B; J Lango; A Rabinovich; P Whetstone; B Hammock (2006). "The neutralizing effect of a polyclonal antibody raised against the N-terminal eighteen-aminoacid residues of birtoxin towards the whole venom of Parabuthus transvaalicus".Toxicon.47 (2):144–149.Bibcode:2006Txcn...47..144I.doi:10.1016/j.toxicon.2005.08.018.ISSN0041-0101.PMID16356521.
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