Practice question

Sensitivity to alpha-amanitin toxin distinguishes three nuclear polymerases and is exploited in nuclear run-on assays. Pol II shows highest sensitivity, IC50 approximately 0.01 microgram per milliliter, blocked by binding near bridge helix. Pol III requires about ten micrograms per milliliter, intermediate sensitivity, while Pol I remains active even at hundreds of micrograms per milliliter, classified as resistant. Ranking therefore Pol II greater than Pol III greater than Pol I. Structural divergence in funnel domains and trigger loop residues that contact bicyclic peptide explains differential binding affinities and differential toxin susceptibility among polymerases.