α-Amanitin

α-Amanitin is the major toxic bicyclic octapeptide of the Amanita phalloides mushroom that has been used in biochemical research for decades. 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. α-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. α-Amanitin is an inhibitor of Pol III.