Diphthamide is a modified histidine amino acid found in eukaryotic elongation factor 2 (eEF-2). It is ADP-ribosylated by diphtheria toxin, which renders the elongation factor inactive. 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… (More on Diphthamide) |