Scorpion toxin

Na+ K+ Ga + TTX, DDT, veratridine, scorpion toxins, procaine, Hdocaine quinidine, tolbutamide, diazoxide, glyburide, minoxidil nifedipine, diltiazem, verapamil, moUusc and spider toxins ... 

Milnes, J.T., Dempsey, C.E., Ridley, J.M., Crociani, O., Arcangeli, A., Hancox, J.C. and Witchel, H.J. (2003) Preferenhal closed channel blockade of hERG potassium currents by chemically synthesised BeKm-1 scorpion toxin. FEBS Letters, 547, 20-26. 

Figures Comparison of the plant defensin structures Rs-AFP((a), gray, 1ayj)and NaDI ((b), green, 1mr4) with/3-purothionin ((c), magenta, 1 bhp) reveals the structural differences between plant defensins and a//3-thionins. The architecture resembles that of insect defensins, for example, drosomycin ((d), pink, 1 myn) or the scorpion toxin charybdotoxin ((e), yellow, 2crd). The structural similarities become clear in the overlay of Rs-AFP, NaDI, and drosomycin ((f), colors as before).

Arseniev, A.S. and Grishin, E.V. (2002) New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1. The... 

Many scorpion toxins, insect defensins, and enzyme inhibitors are cystine-rich polypeptides containing three to four disulfide bonds. In a large number of these toxins, two cystines are involved in the consensus Cys-(Xaa)1-Cys/Cys-(Xaa)3-Cys framework which is responsible for the common characteristic fold consisting of an a-helix and a two- or three-stranded antiparallel (3-sheet (a 3 3-fold or 3a 3 3-fold). For a review see ref[69]. The overall compact globular structures of these cystine-rich peptides contain the cystine stabilized a-helix motif (Section 6.1.5.1.2) which is further stabilized by a third disulfide bond between the N-terminus and the (3-strand adjacent to the helix and in some cases by an additional fourth disulfide bridge. Due to the presence of the cystine stabilized a-helix motif, a preferred initial formation of this motif followed by its stabilization via the additional disulfides was expected. However, in contrast to what was observed for the cystine peptides containing only the cystine stabilized a-helix motif, simple air oxidation is not successful. 

Apart from AP-A, the best characterized of these polypeptides with respect to its biological activity is Anemonia sulcata toxin II (ATX II) [19]. This molecule is also cardioactive [28], as would be expected from its similarity to AP-A. Renaud et al. [29] have compared the activities of a number of sea anemone and scorpion toxins on isolated rat atria and found that anthopleurin-B (AP-B, also known as Ax II) had the highest potency and the greatest margin between the concentrations necessary for maximal inotropic activity and for provoking arrhythmias (0.3 versus 10 n . It was also found that sodium channels of rat cardiac cells in culture, which have a low affinity for tetrodotoxin (TTX), have a particularly high affinity for Type 1 anemone toxins [29], whereas Type 2 toxins [30] and scorpion toxins [31] had similar affinities for TTX-sensitive and TTX-insensitive channels in rat neuroblastoma cells and skeletal myotubes, respectively. 

The scorpion a-toxins have been shown to bind to site 3 on the voltage-gated sodium channel [24,27,42]. These polypeptides contain up to 70 residues crosslinked by four disulfide bonds, but show no sequence similarity to the anemone polypeptides. Possible structural similarities have been discussed [24], and in a theoretical model of the anemone toxin Bg II, some of the cationic residues were in similar locations to those in the crystal structure of the scorpion toxin Aah II [26]. 

Loret EP, Menendez Soto del Valle R, Mansuelle P, Sampieri F, Rochat H. Positively charged amino acid residues located similarly in sea anemone and scorpion toxins. J Biol Chem 1994 269 16785-16788. 

Catterall WA, Beress L. Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore. J Biol Chem 1978 253 7393-7396. 

Thomsen WJ, Catterall WA. Localization of the receptor site for a-scorpion toxins by antibody mapping implications for sodium channel topology. Proc Natl Acad Sci USA 1989 86 10161-10165. 

Scorpion toxins are polypeptides containing 30-78 amino acids. They have their actions on sodium channels as well as at other locations. Charybodotoxin, from the scorpion Sun es quinquestriatus is a 37 amino acid peptide which has potassium channel blocking activity. The really toxic scorpions are found mainly in Mexico and North Africa. Fatalities usually... 

Scorpion toxin Shift of voltage-dependency of activation... 

At the other end, the extracellular entry way is a site that can be blocked specifically by 35- to 40-residue scorpion toxins.368... 

Figure 30-16 Structures of some neurotoxins that affect ion channels. Other neurotoxins include the Na+, K+-ATPase inhibitor ouabain (Fig. 22-12), batrachotoxin (Fig. 22-12), and picrotoxin (Fig. 22-4). The structure of a scorpion toxin is from Almassy et al.,i9ia that of to conotoxin is from Pallaghy et al.,i35 and that of brevetoxin is redrawn after Shimizu et al.i36...

Ion channels have been purified from several types of excitable cells. The proteins that make up the voltage-gated Na+ channels of brain neurons were first identified by labeling them with reactive derivatives of neurotoxins obtained from scorpions. Intact channels were purified from both brain and muscle after solubilization with detergents. When the purified proteins were incorporated into phospholipid vesicles or planar bilayer membranes, they were found to conduct Na+ across the membrane. The ion specificity of the reconstituted channels and the alterations of the conductance in response to changes in Aift or to various neurotoxins were similar to the properties of the original nerve or muscle membranes. In addition to scorpion toxins, a variety of other specific neurotoxins bind to the purified channels and inhibit their activities. These include tetrodotoxin (a poison obtained from... 

---