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Mushrooms that exist in the Amanita phalloides group are responsible for over 50% of all cases due to mushroom poisoning and 95% of the fatal cases. These mushrooms are justly called ?Death Caps? and ?Destroying Angel? for common names. For the past century their toxins have been studied (11). Alpha Amanitin is one of those toxins and it severely compromises RNA polymerase II. The alpha-amanitin binding site is located directly under the bridge helix that extends between Rpb1 and Rpb2. The residues that interact with this toxin are almost exclusively on the bridge helix. There is an especially strong hydrogen bond interaction with a glutamate (Glu822) on the bridge. The other interactions are hydrogen bonds that are found on the Rpb1 subunit (12). Strangely enough this does not inhibit the binding of NTP or the formation of phosphodiester bonds. Instead it slows the translocation rate dramatically. Normally RNA polymerase can create a transcript at several thousand nucleotides per minute; however, the alpha-amanitin toxin reduces this number to only a few nucleotides per minute (12). As a result protein can not be made fast enough to keep up with the protein turnover rate. Since new proteins can not be made fast enough the body slowly starts to ?eat? itself. In other words the body breaks itself down faster than it can build to maintain a healthy status. This process would take several days and generally results in death. |