Scyllatoxin

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

[edit] Source

Scyllatoxin (also leiurotoxin I) 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. <ref name="Zhu">Zhu Q., Liang S., Martin L., Gasparini S., Me´nez A., Vita C..Role of Disulfide Bonds in Folding and Activity of Leiurotoxin I: Just Two Disulfides Suffice. Biochemistry 2002; 41: 11488-11494. </ref>

[edit] Chemistry

Leiurotoxin I is a 31-residue toxin, 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 ß-sheet, Cys3-Cys21 is bound to an N-terminal segment preceding the helix. Leiurotoxin adopts the ά/β motif. <ref name="Zhu">Zhu Q., Liang S., Martin L., Gasparini S., Me´nez A., Vita C..Role of Disulfide Bonds in Folding and Activity of Leiurotoxin I: Just Two Disulfides Suffice. Biochemistry 2002; 41: 11488-11494. </ref> Especially the positively charged residues (Arg6 and Arg13, which are located in the ά helix) are important for the expression of toxin biological activities<ref name="Sabatier">Sabatier J.M., Lecomte C., Mabrouk K., Darbon H., Oughideni R., Canarelli S., Rochat H., Martin-Eauclaire M.F., Van Rietschoten J. 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 1996; 35: 10641-10647.</ref> and for its receptor affinity. <ref name="Buisine">Buisine E. Wieruszeski J.M., Lippens G., Wouters D., Tartar A., Sautiere P. 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. 1997;49:545-55 </ref>

[edit] Target

Scyllatoxin is a blocker of small-conductance Ca2+– activated K+ channels at 10-13 – 10-11 M concentrations in various cell types. <ref name="Zhu"> Zhu Q., Liang S., Martin L., Gasparini S., Me´nez A., Vita C..Role of Disulfide Bonds in Folding and Activity of Leiurotoxin I: Just Two Disulfides Suffice. Biochemistry 2002; 41: 11488-11494. </ref> This toxin shows similarity in its physiological activity and binding specificity to apamin <ref name="Zhu"> Zhu Q., Liang S., Martin L., Gasparini S., Me´nez A., Vita C..Role of Disulfide Bonds in Folding and Activity of Leiurotoxin I: Just Two Disulfides Suffice. Biochemistry 2002; 41: 11488-11494. </ref>, but both toxins show no structural similarity. <ref name="Chicchi"> Chicchi G.G., Gimenez-Gallego G., Ber E. Garcia M.L. Winquist R. Cascieri M.A. Purification and characterization of a unique, potent inhibitor of apamin binding from Leiurus quinquestriatus hebraeus venom. J. Biol. Chem. 1988; 21: 10192-7. </ref>

[edit] Mode of action

Scyllatoxin blocks the slow after-hyperpolarization that follows an action potential in some nerve cells. <ref name="Zhu">Zhu Q., Liang S., Martin L., Gasparini S., Me´nez A., Vita C..Role of Disulfide Bonds in Folding and Activity of Leiurotoxin I: Just Two Disulfides Suffice. Biochemistry 2002; 41: 11488-11494. </ref>

[edit] Toxicity

Scyllatoxin induces spontaneous contractions in guinea pig taenia coli muscle cells that have been relaxed with epinephrine. <ref name="Auguste"> Auguste P., Hugues M., Mourre C., Moinier D., Tartar A., Lazdunski M.. Scyllatoxin, a Blocker of Ca2+-Activated K+ Channels: Structure-Function Relationships and Brain Localization of the Binding Sites. Biochemistry 1992; 31:648-654.</ref>

[edit] Treatment

[edit] References

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