BmKAEP (or anti-epilepsy peptide) is a neurotoxin from the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

of the Manchurian scorpion ''(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

NCBI The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...

Protein Database, the full name of this peptide is listed as "Toxin BmKAEP".

Sources

BmKAEP is one of the components of ''Mesobuthus martensii''′s venom, a well-known scorpion belonging to the family

Buthidae The Buthidae are the largest family of scorpions, containing about 100 genera and 1339 species as of 2022. A few very large genera (''Ananteris'', '' Centruroides'', '' Compsobuthus'', or '' Tityus'') are known, but a high number of species-poor ...

, 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 In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

(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.

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-gated 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 An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

Toxicity

BmK venom induces a transient phase of contraction followed by a slow progressive

flaccid paralysis Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associ ...

in insect larvae. However, since it requires a high dosage to be effective, its toxicity is weak, both in insects and mammals.

Therapeutic use

Though the exact mechanism of its anti-epilepsy effect is not clear, several studies have shown that BmKAEP can inhibit

coriaria ''Coriaria'' is the sole genus in the family Coriariaceae, which was described by Linnaeus in 1753. It includes 14 species of small trees, shrubs and subshrubs, with a widespread but disjunct distribution across warm temperate regions of the w ...

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

-induced

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

in rats by prolonging the latent epilepsy period, relieving the degree of

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

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 Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action ...

to treat several neuronal diseases, such as several types of paralysis,

apoplexy Apoplexy () is rupture of an internal organ and the accompanying symptoms. The term formerly referred to what is now called a stroke. Nowadays, health care professionals do not use the term, but instead specify the anatomic location of the bleedi ...

and epilepsy.

References

External links

* NCBI Protein Database for "Toxin BmKAEP"
AEP1_MESMA, ACCESSION: P15228.2, GI:37999913
{{DEFAULTSORT:Bmkaep Neurotoxins Ion channel toxins Scorpion toxins