Diphtheria Toxin - Mechanism

Mechanism

The diphtheria toxin has the same mechanism of action as the enzyme NAD(+)—diphthamide ADP-ribosyltransferase (EC 2.4.2.36). It catalyzes the transfer of NAD+ to a diphthamide residue in eukaryotic elongation factor-2 (eEF2), inactivating this protein. It does so by ADP-ribosylating the unusual amino acid diphthamide. In this way, it acts as a RNA translational inhibitor. The catalysed reaction is as follows:

NAD+ + peptide diphthamide nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide

The cholera toxin and exotoxin A of Pseudomonas aeruginosa uses a similar mechanism of action.

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