α-Amanitin has an unusually strong and specific attraction to the enzyme RNA polymerase II. Upon ingestion and uptake by liver cells, it binds to the RNA polymerase II enzyme, effectively causing cytolysis of hepatocytes (liver cells).
How does a Amanitin inhibit RNA polymerase?
α-Amanitin-Inhibiting RNA Polymerases II and III
Amanitin binds with high specificity and high affinity (Ki = 3–4 nM) near the catalytic active site of RNAP II. It traps a conformation of the enzyme that prevents nucleotide incorporation and translocation of the transcript.
How does Alpha Amanitin affect transcription?
Alpha amanitin inhibits RNA polymerase II (pol II) by blocking initiation and elongation of transcription. It has been shown to bind the pol II beneath the bridge helix and across the cleft between Rpb1 and Rpb2 (1). Most of the residues of pol II that actually interact are on the bridge helix.