Talk:Diphthamide

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It is usually found at position H715 in mammalian eEF2 (H699 in yeast). This residue is modified by the protein encoded by the DPH1 (OVCA1) gene. Dph1 knockout mice are inviable while heterozygotes develop diverse types of carcinomas and sarcomas. In humans, DH1 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 an ADP-ribosylated by diphtheria toxin, hence the name, which renders the elongation factor inactive. Nicotinamide adenine dinucleotide (NAD) serves as its ADP-ribosyl donor. The inactivation of the elongation factor results in a halt in protein synthesis, which in turn leads to cell death. Diphthamide consists of seven genes namely DH1, DH2, DH3, DH4, DH5, DH6, and DH7. According to research conducted by Sebastian Stahl et al., the loss of diphthamide or presence of unmodified eEF2 does not severely impact cell growth under normal conditions. However, animals with homozygous DPHko do not survive beyond embryonic stages, suggesting that the diphthamide may be necessary for development.