Bukatoxin
Encyclopedia
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, α-scorpion toxins prolong action potential
s.
that is expressed and secreted by the venom gland of the scorpion Buthus martensii
Karsch (Chinese Scorpion).
with 8 cysteines
(at positions 12, 16, 22, 26, 36, 46, 48 and 63) that are linked by four disulfide bridges
. The molecular weight
of the neurotoxin is 7.2 kDa.
Bukatoxin is a member of the 4C-C scorpion toxin superfamily
. It can be further categorized as a polypeptide
gating modifier toxin that belongs to the α-subfamily of scorpion neurotoxins.
site 3 of sodium channels, thereby prolonging the action potential.
of bukatoxin, the 52PDKVP 56 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 DKV 55, 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 Val 1 and Asp 9, 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.
, but the mechanisms are not sodium channel-mediated and not completely elucidated as of yet.
Scorpion toxin
Scorpion toxins are proteins found in the venom of scorpions. Their toxic effect may be mammal or insect specific, and acts by binding to sodium channels, inhibiting the inactivation of activated channels and blocking neuronal transmission....
found in the venom of the Chinese scorpion Buthus martensi Karsch. By blocking the inactivation of sodium ion channels, α-scorpion toxins prolong action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
s.
Source
Bukatoxin (short names: BukaTx or BKTx, alternative name: BuK-alpha-Tx) is a neurotoxinNeurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
that is expressed and secreted by the venom gland of the scorpion Buthus martensii
Mesobuthus martensii
Mesobuthus martensii is a species of scorpion in the family Buthidae. Its common names include Chinese scorpion, Manchurian scorpion, Chinese armor-tail scorpion and Chinese golden scorpion. Despite its common name, this scorpion is not only found in Manchuria or China, but also in Mongolia, Korea...
Karsch (Chinese Scorpion).
Chemistry
Bukatoxin has a linear sequence of 65-residue amino acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
with 8 cysteines
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
(at positions 12, 16, 22, 26, 36, 46, 48 and 63) that are linked by four disulfide bridges
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
. The molecular weight
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...
of the neurotoxin is 7.2 kDa.
Bukatoxin is a member of the 4C-C scorpion toxin superfamily
Taxonomic rank
In biological classification, rank is the level in a taxonomic hierarchy. Examples of taxonomic ranks are species, genus, family, and class. Each rank subsumes under it a number of less general categories...
. It can be further categorized as a polypeptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
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 receptorReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
site 3 of sodium channels, thereby prolonging the action potential.
Mode of Action
The region between 52 and 56 in the amino acid sequencePeptide sequence
Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain in peptides and proteins. The sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing free carboxyl group...
of bukatoxin, the 52PDKVP 56 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
Tripeptide
A tripeptide is a peptide consisting of three amino acids joined by peptide bonds.Examples of tripeptides are:*Eisenin is a peptide with immunological activity that is isolated from the Japanese marine alga, Eisenia bicyclis, which more commonly is known as, Arame*GHK-Cu is a human copper binding...
segment 53 DKV 55, 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 Val 1 and Asp 9, 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
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
segment during depolarization. As a result, inactivation of the channel becomes slower, leading to a broadened action potential.
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 . Muscle relaxation effects also arise in rabbit corpus cavernosumCorpus cavernosum penis
The corpus cavernosum penis is one of a pair of sponge-like regions of erectile tissue which contain most of the blood in the penis during penile erection...
, but the mechanisms are not sodium channel-mediated and not completely elucidated as of yet.