BmKAEP
BmKAEP (or anti-epilepsy peptide) 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.
Etymology
[edit | edit source]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 NCBI Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".[1]
Sources
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BmKAEP is one of the components of Mesobuthus martensii's venom,[2] a well-known scorpion belonging to the family Buthidae, which is found distributed throughout Eastern Asia and China.
Chemistry
[edit | edit source]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.[3]
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).[3] 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.[3] Its lysine residue, at position 51, also has a special feature: it interacts with mammalian Na+ channels.[4]
| BmKAEP primary sequence[5] |
|---|
|
01 mklflllvis asmlidglvn adgyirgsng |
Target and Mode of Action
[edit | edit source]Because of its sequence homology with other β-toxins, BmKAEP is predicted to bind to site 4 (S4) of voltage-gated Na+ channels, at domains I, III and IV.[6] 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,[7] 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 potentials.[2]
Toxicity
[edit | edit source]BmK venom induces a transient phase of contraction followed by a slow progressive flaccid paralysis in insect larvae.[8] However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.[9]
| Toxicity parameters | |
|---|---|
| LD50 | 2,4 mg/kg (mice; intraperitoneal injection)[3] |
| MLD (minimum lethal dose) | 0,074 mg/kg (mice; Intracerebroventricular injection)[2] |
| CPU (concentration paralysis unit) | 1 μg/body (larvae)[2] |
| NOAEL (No observed adverse effect) | <2 μg (insects); <20 μg (mice)[3] |
Therapeutic use
[edit | edit source]Though the exact mechanism of its anti-epilepsy effect is not clear, several studies have shown that BmKAEP can inhibit coriaria 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.[9]
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.[2]
References
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- ^ Universal protein resource accession number P15228 for "Toxin BmKAEP" at UniProt.
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External links
[edit | edit source]- NCBI Protein Database for "Toxin BmKAEP": AEP1_MESMA, ACCESSION: P15228.2, GI:37999913
