Diphthamide

Diphthamide is a modified histidine amino acid found in eukaryotic elongation factor 2 (eEF-2).

It is usually found at position H715 in mammalian eEF2 (H699 in yeast). This residue is modified by the protein encoded by the OVCA1 gene (homolog of DPH1 in mice). DPH1 knockout mice are inviable while heterozygotes develop diverse types of carcinomas and sarcomas. In humans, OVCA1 is frequently found mutated in ovarian cancer. Loss of heterozygosity has taken place in 50% of benign tumours, and 90% of end-stage ovarian tumours.

It is ADP-ribosylated by diphtheria toxin, hence the name, which renders the elongation factor inactive.