Evil enzymes and biochemical bombs
Now that I have covered the ripper toxins and neurotoxins, it is time to take about enzymes. Ah, enzymes. They help digest food, catalyze important reactions, destroy pathetic prey—yes, anemones and other venomous animals have somehow managed to use enzymes to kill things. In anemones, there are two major kinds of enzymes which are classified as toxins: phospholipases A2 (PLA2s) and metalloproteases. Aside from anemones, metalloproteases are also found in as snakes and ticks. These diabolical toxins cause hemorrhage and necrosis by destroying the extracellular matrix (ECM). The ECM is a vital piece of biological architecture which provides structural and biochemical support for cells. It is composed of collagen, enzymes, and glycoproteins. All of these lovely proteins get degraded by the anemone’s merciless metalloproteases.
Not only do anemone wreck cells with ripper toxins and use neurotoxins to attack ion channels, but they also destroy the support structure for cells. Why not attack cell membranes and myelin with phospholipases A2 (PLA2s)?
PLA2 toxins catalyze the hydrolysis of 2-acyl ester bonds glycerophospholipids. Yes, even the cell membranes aren’t safe from an anemone’s venom. The funny thing is that your pancreas uses PLA2 to digest that sandwich you had for breakfast, but a lot of venomous animals use PLA2 to kill things. PLA2 toxins could serve a bunch of different roles like defense, immobilization, and digestion. The literature suggests that PLA2 could play multiple roles which makes it a bit to tricky study the structure-function relationship of these toxins.
Figure 1: Predicted strcuture of UcPLA2. The toxin was isolated from the starlet sea anemone (Nematostella vectensis) [Source: Razpotnik, A. et al, 2010]
Just like potassium channel toxins are classified based on structure, PLA2 toxins are also classified based on structural features into four categories: phospholipase A1, phospholipase B, phospholipase C, and phospholipase D. There is a secreted family of PLA2 which need calcium ions to be active. There are certain types of PLA2’s which are found in the cytosol. They can depend on calcium ions for activity, or they can be strong independent enzymes.
Aside from a dash of potent peptides anemone venom has other intresting ingredients.
You see, almost every component in the anemone’s venom plays a part in making sure that the prey or predator dies a slow and excruciatingly painful death. In some cases, anemone venom can also have a pinch of 5-hydroxytryptamine (5-HT, serotonin), histamine, bunodosine, and caissarone. 5-HT enhances vasodilation which enhances the impact of all the other toxins and histamine is excellent for causing sharp pain within victims. Bunodosine is an N-acylamino acid which has analgesic activity, and it targets serotonin receptors. Caissarone is a purine derivative which acts as an antagonist against adenosine receptors. The antagonistic adventures of this lovely ligand involve blocking or dampening the activity of adenosine receptors. You know what else acts as an antagonist against adenosine receptors?
Figure 2: Bunodosoma cangicum (left). Chemical structure of bunodosine (right). [Soruce: Zaharenko, A. J. et al, 2011]
Most of my blog posts in Anemone toxins 101 focus on the toxins, but there are other exciting ligands in anemone venom which aren’t peptides. Bunodosine and caissarone could be developed into some pretty potent marine drugs. Even though I am fascinated with the biomedical applications of anemone toxins specifically, I think other components of the venom shouldn't be glossed over.
Next time, I will talk about the—New Kids on the Block.
Jouiaei, M., Yanagihara, A. A., Madio, B., Nevalainen, T. J., Alewood, P. F., & Fry, B. G. (2015). Ancient venom systems: A review on cnidaria toxins. Toxins, 7(6), 2251–2271. http://doi.org/10.3390/toxins7062251
Lehtonen, J. Y., & Kinnunen, P. K. (1995). Phospholipase A2 as a mechanosensor. Biophysical journal, 68(5), 1888-94.
Razpotnik, A. et al. A new phospholipase A2 isolated from the sea anemone Urticina crassicornis - Its primary structure and phylogenetic classification. FEBS J. 277, 2641–2653 (2010).
Zaharenko, A. J. et al. Bunodosine 391: An Analgesic Acylamino Acid from the Venom of the Sea Anemone Bunodosoma cangicum. J. Nat. Prod. 74, 378–382 (2011).
