Practice question

Alpha-amanitin cyclic octapeptide from Amanita phalloides death cap mushroom penetrates hepatocytes and binds with extremely high affinity in funnel and trigger loop beneath RNA polymerase II active site, obstructing translocation and nucleotide incorporation, leading to slow elongation arrest and degradation of RPB1 subunit. RNA polymerase II is most sensitive with inhibition constant around ten nanomolar, blocked at one microgram per milliliter, causing fatal liver failure. Polymerase III requires tenfold higher concentration, while polymerase I and mitochondrial polymerase resist up to high doses due to structural differences.