Alpha amanitin is a toxin that is found in the mushroom known as the Death Cap.  As the name implies it is very toxic and is one of the most toxic fungi.  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.  There are hydrogen bonds between bridge helix residue 822 and the hydroxypoline 2 of amanitin.  There are also hydrogen bonds between the region of Rpb1 adjacent to the bridge helix and amanitin (1).  These hydrogen bonds help to hold the bridge helix in a way in which it cannot move.  Amanitin does not affect the ability of NTPs to bind.  The fact that bridge helix’s movement is inhibited means that translocation is inhibited.  It has been shown that the rate of translocation lowers from thousands of nucleotides per minute to only a few nucleotides per minute (1).

RNA polymerase II bound to amanitin. PDB 1K83

The hydrogen bonds between amanitin and the bridge helix. PDB 1K83