BmKAEP
BmKAEP (or anti-epilepsy peptide) is a neurotoxin from the venom of the Manchurian scorpion (Mesobuthus martensii). It is a
Etymology
[edit]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
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Mesobuthus_martensii_%28283%29.jpg/220px-Mesobuthus_martensii_%28283%29.jpg)
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]BmKAEP is an inhibitory
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] |
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01 mklflllvis asmlidglvn adgyirgsng |
Target and Mode of Action
[edit]Because of its sequence homology with other
Toxicity
[edit]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 |
NOAEL (No observed adverse effect) | <2 |
Therapeutic use
[edit]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
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
[edit]- ^ "Toxin BmKAEP". NCBI. Retrieved 25 October 2010.
- ^ a b c d e Goudet C, Chi CW, Tytgat J (September 2002). "An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch". Toxicon. 40 (9): 1239–58. doi:10.1016/S0041-0101(02)00142-3. PMID 12220709.
- ^ a b c d e Wang CG, He XL, Shao F, Liu W, Ling MH, Wang DC, Chi CW (April 2001). "Molecular characterization of an anti-epilepsy peptide from the scorpion Buthus martensi Karsch". European Journal of Biochemistry. 268 (8): 2480–5. doi:10.1046/j.1432-1327.2001.02132.x. PMID 11298767.
- ^ Yuan Y, Luo L, Peigneur S, Tytgat J, Zhu S (July 2010). "Two recombinant depressant scorpion neurotoxins differentially affecting mammalian sodium channels". Toxicon. 55 (8): 1425–33. doi:10.1016/j.toxicon.2010.02.019. PMID 20219516.
- ^ Universal protein resource accession number P15228 for "Toxin BmKAEP" at UniProt.
- ^ Cestèle S, Catterall WA (2000). "Molecular mechanisms of neurotoxin action on voltage-gated sodium channels". Biochimie. 82 (9–10): 883–92. doi:10.1016/S0300-9084(00)01174-3. PMID 11086218.
- ^ Cestèle S, Qu Y, Rogers JC, Rochat H, Scheuer T, Catterall WA (October 1998). "Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II". Neuron. 21 (4): 919–31. doi:10.1016/S0896-6273(00)80606-6. PMID 9808476.
- ^ Gurevitz M, Froy O, Zilberberg N, Turkov M, Strugatsky D, Gershburg E, Lee D, Adams ME, Tugarinov V, Anglister J, Shaanan B, Loret E, Stankiewicz M, Pelhate M, Gordon D, Chejanovsky N (November 1998). "Sodium channel modifiers from scorpion venom: structure-activity relationship, mode of action and application". Toxicon. 36 (11): 1671–82. doi:10.1016/S0041-0101(98)00160-3. PMID 9792184.
- ^ a b Zhou XH, Yang D, Zhang JH, Liu CM, Lei KJ (January 1989). "Purification and N-terminal partial sequence of anti-epilepsy peptide from venom of the scorpion Buthus martensii Karsch". The Biochemical Journal. 257 (2): 509–17. doi:10.1042/bj2570509. PMC 1135608. PMID 2930463.
External links
[edit]- NCBI Protein Database for "Toxin BmKAEP": AEP1_MESMA, ACCESSION: P15228.2, GI:37999913