Diphthamide

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.

Structure and biosynthesis

Diphthamide is proposed to be a 2-[3-carboxyamido-3-(trimethylammonio)propyl]histidine. Though this structure has been confirmed by X-ray crystallography, its stereochemistry is uncertain.

Diphthamide is biosynthesized from histidine and S-adenosyl methionine (SAM). The side chain bound to imidazole group and all methyl groups come from SAM. The whole synthesis takes place in three steps:

• transfer of 3-amino-3-carboxypropyl group from SAM
• transfer of three methyl groups from SAM – synthesis of diphtine
• amidation – synthesis of diphthamide

In eukaryotes, this biosynthetic pathway contains a total of 7 genes (Dph1-7).

Biological function

Diphthamide ensures translation fidelity.

The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways.

References