Practice question

Alpha-amanitin is bicyclic octapeptide toxin from Amanita phalloides and related mushrooms selectively inhibiting RNA polymerases with highest affinity for Pol II. Toxin binds deep within funnel below bridge helix near trigger loop blocking translocation along DNA and nucleotide entry, trapping polymerase in pre-translocated state halting mRNA synthesis causing liver failure. Pol III inhibited at micromolar, Pol I resistant allowing discrimination. Amanitin used experimentally to stall complexes for cryo-EM, study transcription kinetics, and generate resistant Pol II mutants mapping binding pocket residues informing mechanism and polymerase evolution.