Virtuelle (Nano) Welten: PDB Molecule of the Month 28: Anthrax Toxin

Lethal Factor and Edema Factor

The two toxic components of anthrax toxin are both enzymes that attack the signalling functions of the cell. Once they are delivered inside by the protective antigen, they set to work. The edema factor (shown on the left) is an adenyl cyclase enzyme. It takes ATP (in green) and clips off two phosphates, reconnecting the remaining one back in a small loop to form cyclic AMP. Cyclic AMP is an important messenger in cells, often used to relay messages that are sent by hormones. For instance, a rise in cyclic AMP in response to adrenaline can cause an increase in heart rate. Edema factor floods the cell with cyclic AMP, destroying the careful balance normally achieved by hormones.

The lethal factor (shown on the right) attacks at another sensitive spot. It is a very specific protease that makes a cut in several similar mitogen-activated protein kinase kinases. In the illustration, a small segment of this target is shown in green, bound in the active site of the toxin. These kinases are essential steps at the end of another signalling pathway which is important in cell growth and proliferation. The lethal factor destroys this control by disabling one key step in the chain of messsages.