BmKAEP
Encyclopedia
BmKAEP is a neurotoxin
from the venom
of the Manchurian scorpion
(Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.
Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".
BmKAEP is one of the components of Mesobuthus martensii′s venom, a well-known scorpion belonging to the Buthidae
family, which is found distributed throughout Eastern Asia and China.
BmKAEP is a 61-amino-acid protein derived from an 85-amino-acid precursor. The mature protein contains 8 cysteine residues that establish 4 disulfide bridges (4C-C). Despite its high homology with other depressant toxins, BmKAEP differs from them at residues 6, 7 and 39, which is thought to be important in determining its unique function. Its lysine residue, at position 51, also has a special feature: it interacts with mammalian Na+ channels.
Na+ channels, at domains I, III and IV. Its interaction with the S4 loop causes the loop to be maintained at the outward activated position. Therefore, activation of the Na+ channels shifts towards more negative values, enhancing the channel's activation and promoting spontaneous and repetitive firing. Subsequently, the sodium current amplitude decreases, due to the membrane potential depolarization, thus suppressing action potential
s.
in insect larvae. However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.
lactone
-induced epilepsy
in rats by prolonging the latent epilepsy period, relieving the degree of seizures and shortening its average duration, at a pharmacological dosage of only 0,057 µg/g.
Mesobuthus martensii, especially its tail, has been used in Chinese traditional medicine to treat several neuronal diseases, such as several types of paralysis
, apoplexy
and epilepsy.
Neurotoxin
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...
from the venom
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...
of the Manchurian scorpion
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...
(Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.
Etymology
BmK is the abbreviation for Buthus martensi Karsch, an old name for the scorpion that is the source of BmKAEP; AEP is an abbreviation for anti-epilepsy peptide. At the NCBINational Center for Biotechnology Information
The National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".
Source
Buthidae
Buthidae is the largest family of scorpions, containing about 80 genera and over 800 species as of mid-2008. Its members are known as, for example, thick-tailed scorpions and bark scorpions. There are a few very large genera , but also a high number of species-poor or monotypic ones...
family, which is found distributed throughout Eastern Asia and China.
Chemistry
BmKAEP is an inhibitory β-toxin and thus, a Na+ channel inhibitor. As with other mammal and insect toxins, BmKAEP is classified according to species and mechanism of action.BmKAEP is a 61-amino-acid protein derived from an 85-amino-acid precursor. The mature protein contains 8 cysteine residues that establish 4 disulfide bridges (4C-C). Despite its high homology with other depressant toxins, BmKAEP differs from them at residues 6, 7 and 39, which is thought to be important in determining its unique function. Its lysine residue, at position 51, also has a special feature: it interacts with mammalian Na+ channels.
| [Source: UniProt UniProt UniProt is a comprehensive, high-quality and freely accessible database of protein sequence and functional information, many of which are derived from genome sequencing projects... ] |
|---|
01 mklflllvis asmlidglvn adgyirgsng 31 ckvsclwgne gcnkeckafg ayygycwtwg 61 lacwceglpd dktwksesnt cggkk |
Target and Mode of Action
Because of its sequence homology with other β-toxins, BmKAEP is predicted to bind to site 4 (S4) of voltage-gatedVoltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....
Na+ channels, at domains I, III and IV. Its interaction with the S4 loop causes the loop to be maintained at the outward activated position. Therefore, activation of the Na+ channels shifts towards more negative values, enhancing the channel's activation and promoting spontaneous and repetitive firing. Subsequently, the sodium current amplitude decreases, due to the membrane potential depolarization, thus suppressing 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.
Toxicity
BmK venom induces a transient phase of contraction followed by a slow progressive flaccid paralysisFlaccid paralysis
Flaccid paralysis is a clinical manifestation characterized by weakness or paralysis and reduced muscle tone without other obvious cause .-Polio:...
in insect larvae. However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.
| Toxicity parameters | |
|---|---|
| 2,4 mg/kg (mice; intraperitoneal injection) | |
| MLD Minimum lethal dose Minimum lethal dose is the least amount of drug that can produce death in a given animal species under controlled conditions.For the concept Median Lethal Dose , see Median lethal dose.... (minimum lethal dose) |
0,074 mg/kg (mice; Intracerebroventricular injection) |
| CPU (concentration paralysis unit) | 1 µg/body (larvae) |
| NOAEL (No observed adverse effect) | <2 µg (insects); <20 µg (mice) |
Therapeutic use
Though the exact mechanism of its anti-epilepsy effect is not clear, several studies have shown that BmKAEP can inhibit coriariaCoriaria
Coriaria is the sole genus in the family Coriariaceae. It includes about 30 species of subshrubs, shrubs and small trees, with a widespread but disjunct distribution across warm temperate regions of the world, occurring as far apart as the Mediterranean region, southern and eastern Asia, New...
lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
-induced epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
in rats by prolonging the latent epilepsy period, relieving the degree of seizures and shortening its average duration, at a pharmacological dosage of only 0,057 µg/g.
Mesobuthus martensii, especially its tail, has been used in Chinese traditional medicine to treat several neuronal diseases, such as several types of paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
, apoplexy
Apoplexy
Apoplexy is a medical term, which can be used to describe 'bleeding' in a stroke . Without further specification, it is rather outdated in use. Today it is used only for specific conditions, such as pituitary apoplexy and ovarian apoplexy. In common speech, it is used non-medically to mean a state...
and epilepsy.
External links
- NCBI Protein Database for "Toxin BmKAEP": AEP1_MESMA, ACCESSION: P15228.2, GI:37999913