Venoms Mamba snake

Ml 2 MT4J (proteins) Mamba snake venom mACh-R allosteric activator agonists... 

Fasciculins] (7 kDa proteins) Dendroaspis angusticeps (mamba snake) venom AChE (at pM-nM)... 

Dajas, F., Bolioli, B., Castello, M.E., Silveira, R. (1987). Rat striatal acetylcholinesterase inhibition by fasciculin (a polypeptide fi-om green mamba snake venom). Neurosci. Lett. 77 87-91. 

Fasciculins Characterized From the Mamba Snake Venoms (Elapidae Family) (Dendroapsis genus)... 

Le Du, M.H., Marchot, R, Bougis, R, et al., 1992. 1.9-A Resolution structure of fasciculin 1, an anti-acetylcholinesterase toxin from green mamba snake venom. J. Biol. Chem. 267, 22122-22130. 

Lee, C.Y., Tsai, M.C., Tsaur, M.L., et al., 1985. Pharmacological study on angus-ticeps-type toxins from mamba snake venoms. J. Pharmacol. Exp. Then 233, 491-198. 

Ludolfph, A.C., 2000. Mamba snake venom. In Spencer, P.S., Schaumburg, H.H., Ludolph, A.C. (Eds.), Experimental and Clinical Neurotoxicology, Oxford University Press, New York, NY, pp. 751. 

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. 

The fasciculins are a family of closely related peptides that are isolated from the venom of mambas and exert their toxic action by inhibiting AChE. The crystal structure of fasciculin 2 from green mamba Dendroaspis angusticeps) snake venom was first resolved in 1992 (Le Du et al., 1992). The three-dimensional (3D) structure of fasciculin 1 obtained from the US National Library of Medicine, National Center for Biotechnology Information, MMDB database is illustrated in Figure 11.2. 

Clinically, mamba bites may not provoke a major local reaction. If neurotoxins are injected by the bite, clinical symptoms appear within minutes to hours. Clinical signs of impairment of neuromuscular transmission (ptosis, ophthalmoplegia, bulbar symptoms, or generalized weakness) dictate administration of antivenom (Ludolfph, 2000). For Elapidae (coral snakes) venom is known that is a potential neurotoxin and may cause paresthesias, weakness, cranial nerve dysfunction, confusion, fasciculations, and lethargy. Often mild local findings, diplopia, ptosis, and dysarthria are common early symptoms. Patients die because of respiratory paralysis. In these cases, early and aggressive... 

Strydom, D.J. (1976). Snake venom toxins. Purification and properties of low-molecular-weight polypeptides of Dendroaspis polylepis polylepis (black mamba) venom. Eur. J. Biochem. 69 169-76. 

In order to explore deeper insight into the mechanism of actions of DHPs, several authors carried out molecular modehng studies on these compounds [52-54]. In a recent molecular modeling study on calcium channel blockers, nifedipine and black mamba toxin FS2 (a venom of the black mamba snake, which has been demonstrated to block the L-type calcium channel [55,56], is a small peptide consisting of 58-74 amino acid residues and having 4-5 intramolecular disulfide bridges formed by cystein residues), Schleifer [54] observed the following ... 

Acetylcholine receptors - muscarinic agonists There are a number of natural plant alkaloid toxins, including arecoline, muscarine and pilocarpine and green mamba snake peptides venoms, including MTl, MT2, MTS and MT4. 

Several of the most poisonous snakes in the world use inhibition of AChE as their means of killing. For example the Black Mamba (Dendroapsis polx/lepis) from Africa secretes fasciculins into its venom. The fasciculins are potent AChE inhibitors and make the Black Mamba s venom amongst the most potent venoms known only 21 mg (equivalent to about three grains of salt) would be needed to kill an average sized person. Indeed, a Hospital in South Africa reported treating seven patients for Mamba bites — all of whom died within 24 hours. The symptoms associated with a Mamba bite are tetany. 

Potassium is found in the fiuids of the body as the K+ ion, and its presence is essentiai to the operation of our nervous system. The passage of impuises aiong the nerves requires the fiow of (and Na+) through channeis in the membranes of the nerve ceiis. Faiiure of this ion fiow prevents nerve transmissions and resuits in death. For exampie, the biack mamba snake kiiis its victims by injecting a venom that biocks the potassium channeis in the nerve ceiis. 

The black mamba snake s venom kills by blocking the potassium channeis in the nerve cells of victims. 

The CE/MS analysis of the venom of the snake Dendroaspis polylepis polylepis, the black mamba, is reported by Tomer and coworkers.A VG 12-250 quad-rupole equipped with a Vestec ESI source (coaxial sheath flow interface) was employed for this experiment. The sheath fluid was a 50 50 methanol 3% aqueous acetic acid solution. The CE voltage was set at -30 kV during the analysis and the ESI needle was held at -h3 kV. The CE running buffer used was 0.01 M acetic acid at pH 3.5. The APS column was flushed with buffer solution for 10 min prior to sample analysis. The snake venom was dissolved in water at a concentration of 1 mg/ml and 50 nl of the analyte solution was injected into the column. They demonstrated the existence of at least 70 proteins from this venom. 

Source From The charaterization of snake venoms using capillary electrophoresis in conjuction with electrospray mass spectronetry Black Mambas, in Electrophoresis. 

Snake venom is modified saliva that is stored in a specialized structure and has been augmented with a series of toxic proteins. Despite the wide array of proteins that may contribute to the toxicity of snake venom (no fewer than twenty-five), the impacts of venom fall loosely into two categories venoms that impair the circulation of blood, and venoms that impair the electrical connections between locomotor nerves and muscles. The pit vipers of the Americas—the ratdesnakes, for example—generally employ venoms that target circulation, while the kraits of Asia and the mambas of Africa employ neurotoxic venom. 

The venom of the mamba snake (Dendroaspis angusticeps, Dendroaspis polylepis, Dendroaspis viridis, Dendroaspis jamesoni) contains a mixture of neurotoxic compounds, including postsynaptic cholinoreceptor a-neurotoxins, dendrotoxins, fasciculins, and muscarinic toxins (Hawgood and Bon, 1991). Effects at the NMJ include AChE inhibition by fasciculins and increased presynaptic release of ACh by dendrotoxins (polypeptides that facilitate ACh release in response to nerve stimulation) together with the high ACh content of mamba toxin (6-24 mg/g), these effects are synergistic and enhance neurotoxicity and lethality. Moreover, the venom may contain other components that have a synergistic action with dendrotoxin. 

FIGURE 30.2 The 3-D protein structure of Fasl derived from green mamba (D. angusticeps) snake venom. Source Image obtained from the public domain at the US National Library of Medicine, Natiorud Center for Biotechnology Information, MMDB. 

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