Bukatoxin is an α- scorpion toxin found in the venom of the Chinese scorpion ''Buthus martensi'' Karsch. By blocking the inactivation of

sodium ion channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...

, α-scorpion toxins prolong action potentials.

Sources

Bukatoxin (short names: BukaTx or BKTx, alternative name: BuK-alpha-Tx) is a

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

that is expressed and secreted by the venom gland of the scorpion ''

Buthus martensii ''Olivierus martensii'' is a species of scorpion in the family Buthidae. Its common names include Chinese scorpion,

Chemistry

Bukatoxin is a 65-residue peptide with the amino acid sequence VRDGYIADDKNCAYFCGRNAYCDEECIINGAESGYCQQAGVYGNACWCYKLPDKVPIRVSGECQQ, and has four disulfide bridges (Cys12-Cys63, Cys16-Cys36, Cys22-Cys46, Cys26-Cys48). The molecular weight of the neurotoxin is 7.2 kDa.{{Cite web, url=https://www.uniprot.org/uniprot/P82815, title = Bukatoxin - Mesobuthus martensii (Manchurian scorpion) Bukatoxin is a member of the 4C-C scorpion toxin

superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...

. It can be further categorized as a

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

gating modifier toxin that belongs to the α-subfamily of scorpion neurotoxins.

Target

Based on its homology to other members of the α-scorpion toxin family, bukatoxin most likely blocks the inactivation of neuronal sodium channels by binding to the neurotoxin

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

site 3 of sodium channels, thereby prolonging the action potential.

Mode of action

The region between 52 and 56 in the amino acid sequence of bukatoxin, the ⁵²PDKVP⁵⁶ loop, interacts with the neurotoxin receptor site 3, which is located on the extracellular loop of sodium channels that connects the S3 and S4 segments on the domain IV. Specifically, the tripeptide segment ⁵³ DKV⁵⁵, which forms a surface loop that is available for binding, is suggested to play a significant role in the blocking of the inactivation of sodium channels. Other residues that could contribute to the binding of bukatoxin to the neurotoxin receptor site 3 of the sodium channels are the Val¹ and Asp⁹, which reside in the same surface loop. The binding of bukatoxin is thought to lead to blocking of conformational changes in the sodium channel, by preventing the outward movement of the IVS4 transmembrane segment during depolarization. As a result, inactivation of the channel becomes slower, leading to a broadened action potential.Catterall W.A., Cestèle S., Yarov-Yarovoy V., Yu F.H., Konoki K., Scheuer T. (2007). Voltage-gated ion channels and gating modifier toxins. ''Toxicon, 49(2)'', 124-141,

Effects

It has been shown that relaxation of carbachol-precontracted rat anococcygeous muscle occurs through the binding of bukatoxin to sodium channels, suggesting that bukatoxin has a muscle relaxation effect. Bukatoxin produces the effects by mediating the activation of nitrergic nerve fibers, most likely via an effect on presynaptic sodium channels.Srinivasan K.N., Nirthanana S, Sasakic T., Satoc K., Chengd B., Gweeb M.C.E., Kinie R.M., Gopalakrishnakonea P. (2001). Functional site of bukatoxin an α-type sodium channel neurotoxin from the Chinese scorpion (Buthus martensi Karsch) venom: probable role of 52PDKVP56 loop. ''FEBS Letters, 494'', 145-149Goudeta C., Chib C.-W., Tytgat J. (2002). An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. ''Toxicon, 40'', 1239-1258Gwee M.C.E, Nirthanan S., Khoo H.-E., Gopalakrishnakone P., Kini R.M., Cheah L.S. (2002). Autonomic effects of some scorpion venoms and toxins. ''Clinical and experimental pharmacology and physiology, 29'', 795-801 Muscle relaxation effects also arise in rabbit corpus cavernosum, but the mechanisms are not sodium channel-mediated and not completely elucidated yet.Teixeira C.E., Ifa D.R., Corso G., Santagada V., Caliendo G., Antunes E., De Nucci G. (2003). Sequence and structure-activity relationship of a scorpion venom toxin with nitrergic activity in rabbit corpus cavernosum. ''The FASEB Journal, 17(3)'', 485-7

References

Scorpion toxins Ion channel toxins Neurotoxins