BotIT2

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BotIT2 is a neurotoxin from the scorpion Buthus occitanus tunetanus, which modifies activation and slows down the deactivation of voltage gated sodium channels. [1]

BotIT2 is found in the venom of the scorpion Buthus occitanus tunetanus (Bot) [2] and hence named Buthus occitanus tunetanus insect toxin 2 (BotIT2).[3]

Chemistry

Structure

N'—DGYIKGYKGCKITCVINDDYCDTECKAEGGTYGICWKWGLACWCEDLPEDKRWKPETNTC –C'
Fig.1 Amino acid sequence of BotIT2 including N-terminus and C-terminus.[2][3]

The BotIT2 peptide is composed of 60 amino-acids (Fig. 1) and its C-terminal residue contains a free carboxyl group. The molecular mass of BotIT2 is 6919 Da.[2][3]

Family

BotIT2 belongs to the Buthidae neurotoxin family. Three main groups are distinguishable in this family: the α-, the β- and the depressant toxins.[4] The BotIT2 has characteristics of all these subgroups.[5] However, BotIT2 is classified as a β-depressant toxin.[3]

Homology

BotIT2 differs from other scorpion toxins not only in its amino acid sequence, but in its effects on activation kinetics of insect sodium channels as well. Similarities are found between BotIT2 and other neurotoxins. For example, the degree of similarity with the α-type and β-type toxins, flaccid-depressive insect toxins and BotIT4 is 30-40%, 60-70%,[1] and 67%,[2] respectively. Despite 67% homogeneity with BotIT4, BotIT4 can be discriminated from BotIT2, by binding two sodium channel sites and having its exclusive depressant electrophysiological function. However, BotIT4 and BotIT2 do share binding characteristics.[1][6]

Target

BotIT2 binds site 4 of voltage gated sodium channels with low capacity (Bmax = 2.4 ± 0.5 pmol/mg) and high affinity (Kd = 0.3 ± 0.1 nM).[1] Besides its influence in insects, BotIT2 affects neuronal membrane properties of mammals as well, but in a less potent way (see Toxicity).[7]

Mode of action

Toxicity

References

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