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Diphthamide synthesis (Step 1) and ADP-ribosylation (Step 2). Dph1 to Dph5 are required for the biosynthesis of diphthamide and are involved in the transfer of a 3-amino-3-carboxypropyl and a methyl group to histidine 715 of eEF-2. The diphthamide imidazole ring is the site for nicotinamide adenine dinucleotide (NAD)+ dependent ADP-ribosylation yielding ADP ribosyl diphthamide.
