Virtuelle (Nano) Welten: PDB Molecule of the Month 40: RNA Polymerase

Poisoning Polymerase

Since RNA polymerase is absolutely essential for the life of the cell, it is a sensitive target for poisons and toxins. The most powerful of these poisons is alpha-amanitin, a small circular peptide created by the death cap mushroom. Eating even one of these mushrooms will lead to coma and death in a manner of days, as the poison attacks RNA polymerase throughout the body. Surprisingly, it binds on the back side of RNA polymerase, away from the active site and away from the binding site for the DNA and RNA. It does not physically block the active site, like most inhibitors, but instead jams the mechanism of the enzyme. RNA polymerase is a highly mobile enzyme, that flexes and changes shape as it performs the sequential steps of binding to DNA, unwinding it, and then building the RNA strand. As seen in PDB entry 1k83, the poison binds between two subunits of the protein, gluing them together and blocking these essential motions.

RNA-Polymerase

Poisoning Polymerase