Cobra toxin

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

Scorpion venoms secretions of the scorpion stinging apparatus. Active principles of S.v. are the neurotoxic scorpamines, which are similar to cobra toxins (see Snake venoms) with respect to M, (6,800-7,200, 4 disulfide bridges, 63-64 amino acid residues of known sequence), amino acid composition (high contents of basic and aromatic amino acids) and activity (both peripheral and central nervous system). The toxin from the North African scorpion, Androc-tonus australia, is one of the most potent known nerve poisons. 

Important toxins are cobramine A and B from cobra toxin and crotactine and crotamine from crotox-in, the toxin of the North American rattlesnake. The toxic proteins are classified according to their mode of action cardiotoxins, neuFotoxins and protease inhibitors (with inhibitory activity toward chymotrypsin and trypsin). Cardiotoxins (heart muscle poisons) cause an irreversible depolarization of the cell membranes of heart muscle and nerve cells. Neurotoxins (nerve poisons) show curare-like activity they prevent neuromuscular transmission by blocking the receptors for the transmitters at the synapses of autonomic nerve endings and at the motor end plate of skeletal muscle. Protease inhibitors inhibit acetylcholine esterase and similar enzymes involved in nerve transmission. 

Five protein-like zones were obtained when cobra toxin was analyzed in paper (Grassmann, 1951). Amanita phalUndea toxin gave two active components (Wieland et al., 1949). A number of other toxins have also been shown to give several components (e.g., Neumann and Habermann, 1952). 

A second group of myotoxic toxins, found almost exclusively in the venoms of cobras, are the cytotoxins (often called cobratoxins, cytolysins, cardiotoxins, or direct lytic factors). These, rather than phospholipases, are almost certainly the primary cause of muscle damage following bites by cobras. Their mechanism of action is not properly known, but it is certainly the case that their action is potentiated by the presence of phospholipases in the venom, even if the phospholipases concerned are not, themselves, myotoxic. The cytotoxins of cobra venom possess no hydrolytic activity of any kind. 

The similarity of the primary structure of different sea snake venoms has already been discussed. Postsynaptic neurotoxins from Elapidae venom have been extensively studied. Elapidae include well-known snakes such as cobra, krait, mambas, coral snakes, and all Australian snakes. Like sea snake toxins, Elapidae toxins can also be grouped into short-chain (Type I) and long-chain (Type II) toxins. Moreover, two types of neurotoxins are also similar to cardiotoxins, especially in the positions of disulfide bonds. However, amino acid sequences between cardiotoxins and sea snake and Elapidae neurotoxins are quite different. In comparing the sequence of sea snake and Elapidae neurotoxins, there is a considerable conservation in amino acid sequence, but the difference is greater than among the various sea snake toxins. 

It is interesting to note that the first demonstration of tyrosinate fluorescence in a protein was made by Szabo et al.au> with two cytotoxins from the Indian cobra Naja naja. While exhibiting different relative amounts of the two emission bands, both toxins had fluorescence at 304 and 345 nm, with the 304-nm band being greatly reduced on excitation at 290 nm. Since these proteins have three tyrosine residues and no tryptophan, it was concluded that the 345-nm emission band was due to tyrosinate. Furthermore, tyrosinate appeared to be formed in the excited state from a hydrogen-bonded ground-state complex based on the absorption spectra. Szabo subsequently reexamined these peptide samples and found that they were contaminated with tryptophan (A. G. Szabo, personal communication). While Szabo s approach to the demonstration of tyrosinate fluorescence was correct based on his initial data, his subsequent finding exemplifies an important caution if tyrosinate emission is suspected, every effort must be made to demonstrate the... 

Toxin-agglutinin fold Erabutoxin, cobra neurotoxin... 

The discovery that the toxins of Elapid snakes bind almost irreversibly to the AChR also facilitated the isolation and study of this receptor. The structure of these venoms has been elucidated those most widely used experimentally are the a-bungarotoxin (BTX) of the Indian cobra and the toxin of the Siamese cobra. These compounds are peptides containing from 61 to 74 amino acids, five disulfide bridges, and a high proportion of basic arginine and lysine residues, often in close proximity. Venoms are toxic because they block cholinergic neurotransmission by binding to the receptor. 

Various types of proteins have been purified using hydrophobic interaction chromatography including alkaline phophatase, estrogen receptors, isolectins, strepavidin, calmodulin, epoxide hydrolase, proteoglycans, hemoglobins, and snake venom toxins (46). In the case of cobra venom toxins, the order of elution of the six cardiotoxins supports the hypothesis that the mechanism of action is related to hydrophobic interactions with the phospholipids in the membrane. 

Theakston RD, Phillips RE, Warrell DA, Galagedera Y, Abeysekera DT et al. (1990) Envenoming by the common krait (bungarus caeruleus) and sri lankan cobra (naja naja naja) efficacy and complications of therapy with haffkine antivenom. Trans R Soc Trap Med Hyg 84 301-8 Thesleff S (1960) Supersensitivity of skeletal muscle produced by botulinum toxin. J Physiol 151 598-607... 

MTLP-1 (= Muscarinic toxin-like protein)] (polypeptide) J raja kaouthia (cobra snake) mACh-R ligand - M3 (Methylscopolamine displacement) (3) [amino acid sequence homology to MTLP-2 from cobra mamba toxins MT1 MT4]... 

Ten per cent of the snakes in the world, about 300 different species, are poisonous, and snakes are an important source of natural toxins. Poisonous snakes belong primarily to certain groups, such as that including the mamba and cobra, the vipers, and the sea snakes and another group that includes the boomslang and the mangrove. 

In the elapids, the group that includes the cobra, a toxin acting on nerves and muscles, a neurotoxin, is responsible for the death of the victim. It causes paralysis of breathing (see box). In addition, the victim will show speech incoordination, the eyelids wiU close, and there wiU be muscle weakness and lack of energy due to the lack of oxygen. About 6 mg of the cobra neurotoxin is sufficient to cause death, which occurs very rapidly, for example a woman in Sri Lanka died fifteen minutes after being bitten by a cobra. 

With cobra venom, the major effect is due to a toxin that acts on the nervous system. This neurotoxin is a small molecule, which can distribute throughout the body rapidly It acts like curare, paralysing the centre in the brain that controls breathing. By acting at the point where nerves control muscles it blocks the transmission of nerve impulses and causes muscle weakness and again affects breathing. The eyelids droop and speech becomes incoordinated. 

In addition, cobra venom contains a toxin that causes changes in the heart rhythm and a loss of blood pressure. Finally a further toxin and a combination of enzymes cause red blood cells to rupture. Thus a bite from the cobra will be rapidly fatal. 

Maybe you could get a good recipe for extracting cobra venom or shell fish toxin through the Freedom of Information Act. 

Eldefrawi and Eldefrawi [98] reported the purification of the acetylcholine of Torpedo electroplax on an affinity column consisting of cobra (Naja naja siamensis) toxin coupled to Sepharose 4B. Desorption with 10 mM benzoquinonium produced a protein that bound [ I]a-bungarotoxin but not [ H]acetyl-choline. However, desorption with 1 mM carbamylcholine gave a receptor protein that bound pH]acetylcholine decamethonium, [ H]nicotine [ C]dimethyl-(-l-)-tubocuranrine, and [ I]a bungarotoxin. Schmidt and Raftery [99] also purified acetylcholine receptor, from Narcine, on a N-(e-aminohexanoyl)-3-aminopropyltrimethyl-ammonium bromide-HBr-agarose column. 

Sine, S.M. Taylor, P. The relationship between agonist occupation and the permeability response of the chohnergic receptor revealed by bound cobra alpha-toxin. J. Biol. Chem. 1980, 225, 10144-10156. 

Acetylcholine receptors provide another target for chemicals with neurotoxic potential most of these act as antagonists. o-Tubocurarine is the classical nicotinic receptor antagonist, and curare-like substances are found in elapid and hydrophid snakes (a-neuro-toxins) such as cobra (a-cobratoxin) and krait... 

That nature is not benign, indeed that it can be extremely deadly, is another lesson to take away from this section. While chemists have been successful in creating some highly lethal agents, none of these quite matches the likes of botulinum toxin, cobra venom or the poison in puffer fish (tetrodotoxin). 

Certain snake toxins have been found to bind irreversibly to the acetylcholine receptor, thus blocking cholinergic transmissions. These include toxins such as alpha-bungarotoxin from the Indian cobra. The toxin is a polypeptide containing 70 amino acids which cross-links the alpha and beta subunits of the cholinergic receptor (see Section 11.14.). 

AChE of high purity and peptide toxins isolated from the venom of cobra Naja naja oxiana are efficacious as prophylactic means in poisonings with orga-nophosphorus inhibitors of ChE [106],... 

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