<unk> s are potent and selective inhibitors of RNA polymerase II, a vital enzyme in the synthesis of messenger RNA (mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA, which is the template for protein synthesis, cell metabolism stops and lysis ensues. The RNA polymerase of Amanita phalloides is insensitive to the effects of<unk> s; thus, the mushroom does not poison itself.<unk> s are able to travel through the bloodstream to reach the organs in the body. While these compounds can damage many organs, damage to the liver and heart result in fatalities. At the molecular level,<unk> s cause damage to cells of these organs by causing perforations in the plasma membranes resulting in misplaced organelles that are normally in the cytoplasm to be found in the extracellular matrix. beta-Amanitin is also an inhibitor of eukaryotic RNA polymerase II and RNA polymerase III, and as a result, mammalian protein synthesis. It has not been found to inhibit RNA polymerase I or bacterial RNA polymerase. Because it inactivates the RNA polymerases, the liver is unable to repair the damage that beta-amanitin causes and the cells of the liver disintegrate and the liver dissolves. α-Amanitin (red) bound to RNA polymerase II from Saccharomyces cerevisiae (brewer's yeast). From . Alpha-amanitin (α-Amanitin) primarily affects the bridge helix of the RNA pol II complex, a highly conserved domain 35 amino acids long. At the N-terminus and the C-terminus of this region there are hinge structures that undergo significant conformational changes throughout the nucleotide addition cycle, and are essential for its progression. One of the many roles of the bridge helix is facilitating the translocation of DNA. Alpha-amanitin binds to the bridge helix of the RNA Pol II complex and it also binds to part of the complex that is adjacent to the bridge helix, while it is in one specific conformation. This binding locks the bridge helix into place, dramatically slowing its movement in translocating the DNA. The rate of pol II translocation of DNA is reduced from several thousand to a few nucleotides per minute.
Amatoxin
Phoratoxin
Aflatoxin
Bukatoxin
Brevetoxin
Eoxin
Ciguatoxin
Dortoxin