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Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2).
Dipthamide is named after the toxin produced by the bacterium Corynebacterium diphtheriae, which targets diphthamide. Besides this toxin, it is also targeted by exotoxin A from Pseudomonas aeruginosa. It is the only target of these toxins.
Diphthamide is biosynthesized from histidine and S-adenosyl methionine (SAM). The side chain bound to imidazole group and all Methyl group come from SAM. The whole synthesis takes place in three steps:
In eukaryotes, this biosynthetic pathway contains a total of 7 genes (Dph1-7).
The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways.
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