Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two subunits linked by disulfide bridges. Binding to the cell surface of the less stable of these two subunits allows the more stable part of the protein to penetrate the host cell.
It catalyzes the ADP-ribosylation eucaryotic elongation factor-2 (eEF2), inactivating this protein. It does so by ADP-ribosylating the unusual aminoacid diphthamide. In this way, it acts as a RNA translational inhibitor. The exotoxin A of Pseudomonas aeruginosa uses a similar mechanism of action.
Diphtheria toxin is extraordinarily potent. The lethal dose for humans is about 0.1 μg/kg of pure protein. A massive release of toxin into the body will likely cause lethal necrosis of the heart and liver.
Diphtheria toxin was discovered in 1890 by Emil Adolf von Bering.
The drug denileukin diftitox uses diphtheria toxin as an antineoplastic agent.