β-Amanitin

β-Amanitin is an extremely toxic constituent of the mushroom, Amanita phalloides, that inhibits Rpb (eukaryotic RNA polymerase II) and eukaryotic RNA polymerase III. This toxin is synthesized as a proprotein, on ribosomes, 34 to 35 amino acids in length and then cleaved at specific proline residues by an enzyme belonging to the prolyl oligopeptidase (POP) subfamily. β-Amanitin shows remarkable binding affinity for eukaryotic RNA polymerase II, slightly binds to RNA polymerase III, and shows no activity on RNA polymerase I; it has been used to determine which types of RNA polymerase are present in a given sample. The toxin works by binding to the bridging helix of RNA polymerase II inhibiting the translocation of RNA and DNA needed to empty the site for the next round of synthesis; thereby slowing the rate of transcription by over 1000 fold.