Scyllatoxin

Scyllatoxin (also leiurotoxin I) is a toxin, from the scorpion Leiurus quinquestriatus hebraeus, which blocks small-conductance Ca²⁺-activated K⁺ channels.

Source

Scyllatoxin is one of the components of the venom of the Israeli scorpion ‘Leiurus quinquestriatus hebraeus’. It consists of only 0.02% of the total protein in crude venom.^[1]

Chemistry

Leiurotoxin I is a 31-residue peptide, with a helix and a short antiparallel β-sheet. This toxin is stabilized by disulfide bonds: Cys8-Cys26 and Cys12-Cys28 is bound to the β-sheet, Cys3-Cys21 is bound to an N-terminal segment preceding the helix. Leiurotoxin adopts the ά/β motif.^[1] Especially the positively charged residues (Arg6 and Arg13, which are located in the ά helix) are important for the expression of toxin biological activities^[2] and for its receptor affinity.^[3]

Target

Scyllatoxin is a blocker of small-conductance Ca²⁺– activated K⁺ channels at 10-13–10-11 M concentrations in various cell types.^[1] This toxin shows similarity in its physiological activity and binding specificity to apamin,^[1] but both toxins show no structural similarity.^[4]

Mode of action

Scyllatoxin blocks the slow after-hyperpolarization that follows an action potential in some nerve cells.^[1]

Toxicity

Scyllatoxin induces spontaneous contractions in guinea pig taenia coli muscle cells that have been relaxed with epinephrine.^[5]

References

1. Zhu Q, Liang S, Martin L, Gasparini S, Ménez A, Vita C (September 2002). "Role of disulfide bonds in folding and activity of leiurotoxin I: just two disulfides suffice". Biochemistry 41 (38): 11488–94. doi:10.1021/bi026136m. PMID 12234192.
2. Sabatier JM, Lecomte C, Mabrouk K, et al. (August 1996). "Synthesis and characterization of leiurotoxin I analogs lacking one disulfide bridge: evidence that disulfide pairing 3-21 is not required for full toxin activity". Biochemistry 35 (33): 10641–7. doi:10.1021/bi960533d10.1021/bi960533d. PMID 8718853.
3. Buisine E, Wieruszeski JM, Lippens G, Wouters D, Tartar A, Sautiere P (June 1997). "Characterization of a new family of toxin-like peptides from the venom of the scorpion Leiurus quinquestriatus hebraeus. 1H-NMR structure of leiuropeptide II". J. Pept. Res. 49 (6): 545–55. doi:10.1111/j.1399-3011.1997.tb01162.x. PMID 9266482.
4. Chicchi GG, Gimenez-Gallego G, Ber E, Garcia ML, Winquist R, Cascieri MA (July 1988). "Purification and characterization of a unique, potent inhibitor of apamin binding from Leiurus quinquestriatus hebraeus venom". J. Biol. Chem. 263 (21): 10192–7. PMID 2839478.
5. Auguste P, Hugues M, Mourre C, Moinier D, Tartar A, Lazdunski M (January 1992). "Scyllatoxin, a blocker of Ca²⁺-activated K⁺ channels: structure-function relationships and brain localization of the binding sites". Biochemistry 31 (3): 648–54. doi:10.1021/bi00118a003. PMID 1731919.