Cobrotoxin

Yang, Chen-Chung. "Crystallization and Properties of the Cobrotoxin from Formosan Cobra Venom." The Journal of Biological Chemistry 240 (1965) 1616-18. 

Since predators of snakes (and humans) have to deal with snake venoms as defenses, they are included here, even though they serve in predation. Snake venoms are primarily enzymes (proteins), especially of the phospholipase A2 type, which breaks down cell membrane phospholipids hydrolytically. Other snake venoms such as cobrotoxin contain peptides with 60-70 amino acid residues. Pharmacologically, they have neurotoxic, cytotoxic, anticoagulant, and other effects. The neurotoxins, in turn, can have pre- or postsynaptic effects. Snake venoms with both neurotoxic and hemolytic effects on the heart are known as cardiotoxins. Cytotoxins attach to the cells of blood vessels and cause hemorrhage. Snake venom factors may stimulate or inhibit blood clotting. Finally, platelet-active factors can contribute to hemorrhage. 

Snakes Phospholipases A2 Proteins, peptides (cobrotoxin), amino acids Neurotoxins... 

Cobra toxin (cobrotoxin), a 62 amino acid protein with four disulfide bridges, causes nondepolarizing blockade at neuromuscular... 

For many who study the chemistry of venoms, the neurotoxins hold particular interest. One example would be the polypeptide toxin cobrotoxin that was isolated from the Formosan cobra and analyzed in 1965 by Chen-Chung Yang, a distingmshed chair professor at Tsing Hua University in Taiwan. The primary structure of this neurotoxin is indicated in Figure 1, along with some components of its secondary structure. There are sixty-two residues in the primary structure and four di-sulfide bonds in the secondary structure. If even one of these di-sulfide bonds is somehow disrupted, the polypeptide is rendered nontoxic. This points to the fact that secondary structure is important even in small polypeptides, not only full-size proteins. 

The action of cobrotoxin arises from its abifity to bind strongly to the receptors in postsynaptic neurons. In order for one nerve cell to signal a neighbor, it releases neurotransmitters that diffuse across a small gap called the synapse. The nerve on the other side of the synapse (the postsynaptic neuron) has proteins that are specifically geared to sense the presence of these neurotransmitters. If these receptors are blocked, the signal is not passed on, and the nerve cell function is disrupted. Cobrotoxin is able to... 

It should be pointed out here that the half inhibition concentration of an irreversible ligand such as aBgt or cobrotoxin, is not an inhibition constant, but a variable depending on the concentration of binding sites in the incubation mixture. As the line between irreversible binding and slowly reversible binding can in practice not always be drawn very accurately, similar considerations may hold for the ionenes... 

Fig. 9. Backbone folding of short neurotoxin molecule as derived from Naja naja neurotoxin II study. Additional contacts from the studies of other neurotoxin are indicated as follows Mos - neurotoxin III Naja mossambica mossambica (36), Erb - erabutoxin b Laticauda semifasciata(40) and Ct - cobrotoxin Naja Naja atra(39). Abbreviation pK -deprotonation of ionogenic group influence on chemical shifts, + - charge effect on pK values, NOE - nuclear Overhauser effect, CS - chemical shift changes upon selective modification, SL - spin label broadening effects.

Chang, C. C., Kawata, Y, Sakiyama, F., and Hayashi, K. (1990). The role of an invariant tryptophan residue in a-bungarotoxin and cobrotoxin. Investigation of active derivatives with the invariant tryptophan replaced by kynurenine. Eur. J. Biochem. 193 567-572. 

Figure 2. Structure of cobrotoxin and a-bungarotoxin showing the amino acid sequence and position of disulfide bonds.

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