Cute but Deadly: The Mechanism of a Snake Venom

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Figure 1: Ted, a green mamba. [Image Link]
This is Ted. Ted is a green mamba snake from southern and western Africa, and despite his super adorable appearance, he’s regarded one of the most venomous snakes in the world. So cute, right?

Green mambas like Ted have a venom that can cause involuntary muscle contractions and death for their victims, by inhibiting acetylcholinesterase at the neuromuscular junction¹. Though not all snake venoms and poisons work in this manner, we’re going to take a closer look at the mechanism by which Ted kills his victims, and why he’s considered one of the deadliest snakes. Go Ted!

Acetylcholine is a major neurotransmitter and chemical modulator in our nervous system. Normally, acetylcholine (ACh) will bind to either muscarinic or nicotinic ACh receptors in different areas in our bodies, and depending on which receptor ACh binds to, an individual can experience a variety of different physiological symptoms¹. When acetylcholine binds to the muscarinic ACh receptors, such as those on parasympathetic neurons, an individual can experience an increase in secretion (of saliva, tears, and urine), heart rate, and breathing rate. On the other hand, when acetylcholine binds to nicotinic ACh receptors, such as those on cholinergic neurons, motor function and overall neurotransmission will be affected¹.

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Figure 2: Fasciculin (yellow) docked on AChE. [Image Link]
Acetylcholine is broken down to two components, acetate and choline, by the enzyme acetylcholinesterase (AChE). Many toxins, nerve agents, and organophosphate pesticides target AChE, preventing it from degrading acetylcholine to acetate and choline like it’s supposed to. The resulting accumulation of ACh causes hyperstimulation at the postsynaptic ACh receptors, and so begins a cascade of things just…exploding from every conceivable orifice. We’re talking vomiting, salivating, urinating, defecating, tremoring, convulsing, and finally, death by respiratory paralysis. Organophosphate nerve agents, like the infamous sarin, inhibit AChE and cause increased cAMP levels that initiate this cascade. Similarly, Ted’s venom, or more precisely, a component of Ted’s venom known as fasciculin, is an inhibitor of acetylcholinesterase² that will paralyze the prey long enough for Ted to swallow. The structure of fasciculin can be seen in the image to the right.

Scientists are continuing to research a way to exploit this little flaw in Ted’s plan. By studying the mechanism, structure, and reversibility of fasciculin, researchers hope to develop antidotes not only for green mamba venom, but for other biotoxins that target AChE as well. So, next time you’re in Africa, say hi to Ted for me — just keep your distance, maybe.

References:

  1. Tai, K, et al. “Mechanism of Acetylcholinesterase Inhibition by Fasciculin: a 5-Ns Molecular Dynamics Simulation.” Journal of the American Chemical Society., U.S. National Library of Medicine, 29 May 2002, http://www.ncbi.nlm.nih.gov/pubmed/12022850.
  2. Radić, Zoran, and Palmer Taylor. “Interaction Kinetics of Reversible Inhibitors and Substrates with Acetylcholinesterase and Its Fasciculin 2 Complex.” Journal of Biochemistry, 17 Oct. 2000, http://www.ncbi.nlm.nih.gov/pubmed/11036076.

 

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