Diphthamide on eukaryotic elongation factor 2 (eEF2 diphthamide)

Diphthamide on eukaryotic elongation factor 2 is a unique, conserved posttranslational modification of a histidine residue in eEF2 found in all eukaryotes and archaea[3][9]. This modification serves as the critical target for ADP-ribosylation by bacterial toxins (such as diphtheria toxin), which disable the function of eEF2, preventing ribosomal translocation and halting protein synthesis[1][3][9]. Its physiological role is to assure the fidelity of mRNA translation, as deficiency leads to translation frameshifts, developmental defects, and increased sensitivity to antimicrobial agents and toxins[3][5][9]. Diphthamide biosynthesis requires several enzymes and is regulated by dedicated pathways[7][9]. The modification is essential for cell viability and development, and loss of diphthamide in humans results in inherited diphthamide-deficiency syndromes[5][3]. It is not a receptor or small molecule drug target but rather a chemically defined site whose alteration or modification plays a central role in cell biology and pathology.

Other names

Diphthamide modificationeEF2-diphthamidePosttranslationally modified histidine on eEF2

ADP-ribosylation of diphthamide by bacterial toxins, inactivating eEF2 and halting protein synthesis. Stalling of eEF2 on ribosomes by fungicides (sordarin)