Alpha Amanitin
α-amanitin is produced by the mushroom Amanita phalloides. α-amanitin binds very tightly to Pol II and disrupts the elongation phase of transcription. α-amanitin can inhibit RNA polymerase II in two ways. It can block the translocation of the transcription complex in the elongation step or it can inhibit the formation of phosphodiester bonds reducing the proficiency of the transcription process8. In RNA Polymerase II in eukaryotes α-amanitin binds beneath the “bridge helix”. The “bridge helix” extends across the cleft between the two largest subunits of Pol II Rpb1 and Rpb2. α-amanitin forms a very strong hydrogen bond between hydroxyproline 2 of α-amanitin and Glu-A822 in the bridge helix. There are also several other hydrogen bonds between α-amanitin and Rpb1 next to the bridge helix2. The binding of α-amanitin to Pol II acts as some what of a barrier to the bridge helix. The binding postion of α-amanitin puts a strain on the movement of the “bridge helix” with respect to the Rpb2 side of the cleft. This strain on the “bridge helix” slows translocation of the Pol II complex from a few thousand nucleotides per minute to just a few nucleotides per minute2.