Snake venom proteins

Peng M, Lu W, Beviglia L, Niewiarowdei S, Kirt EP. Echicetin A snake venom protein that inhibits bindiiigofvonVnilebrand factor and albo gregins to platdet glycoprotein Ib. Blood 1993 81 2321-2328. 

Lit. Chem. Ind. (London) 1995, 914ff. Harding Welch, Venomous Snakes of the World, Oxford Pergamon 1980 J. Toxicol., Toxin Rev. 9, 225 (1990) Lee, Snake Venoms, New York Springer 1979 Nachr. Chem. Tech. Lab. 47,1120 (1999) (review) Naturwiss. Rundsch. 44, 1 (1991) Pharmacol. Ther. 29, 353-405 (1985) 30,91 -113 (1985) 31, 1 -55 (1986) 34,403-451 (1987) 36, l-40(1988) Shier Mebs, Handbook of Toxicology, New York Dekker 1990 Stocker, Medical Use of Snake Venom Proteins, Boca Raton CRC Press 1990 Tu, Handbook of Natural Toxins, Vol.5, New York Dekker 1991 "Tu, Rattlesnake Venoms, New York Dekker 1982. 

Yoshida, E., Fujimura, Y, Miura, S., Sugimoto, M., Fukui, H., Narita, N., Usami, Y, Suzuki, M., and Titani, K., 1993, Alboaggregin-B and botrocetin, two snake venom proteins with highly homologous amino acid sequences but totally distinct functions on von Willebrand factor binding to platelet, Biochem. Biophys. Res. Commun. 191 1386-1392. 

Other Lethal Agents. There are a number of substances, many found in nature, which are known to be more toxic than nerve agents (6). None has been weaponized. Examples of these toxic natural products include shellfish poison, isolated from toxic clams puffer fish poison, isolated from the viscera of the puffer fish the active principle of curare "heart poisons" of the digitaUs type the active principle of the sea cucumber active principles of snake venom and the protein ricin, obtained from castor beans (See Castor oil). 

Figure 2.14 shows examples of both cases, an isolated ribbon and a p sheet. The isolated ribbon is illustrated by the structure of bovine trypsin inhibitor (Figure 2.14a), a small, very stable polypeptide of 58 amino acids that inhibits the activity of the digestive protease trypsin. The structure has been determined to 1.0 A resolution in the laboratory of Robert Huber in Munich, Germany, and the folding pathway of this protein is discussed in Chapter 6. Hairpin motifs as parts of a p sheet are exemplified by the structure of a snake venom, erabutoxin (Figure 2.14b), which binds to and inhibits... 

Protective and exploitive proteins Immunoglobulins Thrombin Eibrinogen Antifreeze proteins Snake and bee venom proteins Diphtheria toxin Rtcin... 

Beta-bungarotoxin, a protein in cobra snake venom, also binds to cholinergic nerves to stop ACh release while a-bungarotoxin (from the same source) binds firmly to peripheral postsynaptic nicotinic receptors. The combined effect ensures the paralysis of the snake s victim. 

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. 

Enzyme reactions. Some toxicants can act as enzymes. A number of natural toxicants operate in this way. For example, snake venoms often contain hydrolytic enzymes, which degrade tissue. Ricin from the castor oil plant is more sophisticated and causes the hydrolytic destruction of ribosomes, so disrupting protein synthesis. 

In addition to the proposed regulatory role of ATP and pyrophosphate, some possibility exists that 3, 5 -cyclic phosphate diesterase is under physiological control. Such ideas arose through observations of Cheung (43, 62) that the partially purified enzyme from beef brain was markedly activated by snake venom. The stimulatory factor was labile at extreme pH it was not dialyzable and appeared to be a protein. A similar activating factor is also present in brain tissue (63) and is removed during purification of the diesterase. It seems to interact stoichiometrically with the enzyme. The activator is destroyed by trypsin and is not proteolytic itself. The precise role of this protein in regulating the phosphodiesterase in vivo is not yet established, however. 

Snake venoms contain many types of lipases, including phospholipase A2. Why do small amounts of this enzyme contribute to some of the toxic effects of snake venom (Bee venom contains a protein that stimulates phospholipase A2.)... 

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. 

Toxic proteins Serve as a defense for the plant or animal Snake venoms ... 

When the Tg lesions is opened by ammonolysis, the resulting product (ureidoisobutyric acid) inhibits snake venom phosphodiesterase, A exonuclease and the Klenow (exo ) fragment (Matray et al. 1995 see also Greenberg and Matray 1997). It is, however, removed by E. coli Fpg and Nth proteins (Jurado et al. 1998). 

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