Diphtheria toxin

Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae, the pathogen bacterium that causes diphtheria.

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Structure

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.^[1]

Mechanism

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.

Lethal dose

Diphtheria toxin is extraordinarily potent.^[1] The lethal dose for humans is about 0.1 μg of toxin per kg of bodyweight. A massive release of toxin into the body will likely cause lethal necrosis of the heart and liver.^[2]

History

Diphtheria toxin was discovered in 1890 by Emil Adolf von Bering.

Clinical use

The drug denileukin diftitox uses diphtheria toxin as an antineoplastic agent.

References

1. ^ ^{a b} Murphy JR (1996). Corynebacterium Diphtheriae: Diphtheria Toxin Production In: Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1. 
2. ^ Pappenheimer A (1977). "Diphtheria toxin.". Annu Rev Biochem 46: 69-94. PMID 20040.