A mutation in codon 717 of the CHO-K1 elongation factor 2 gene prevents the first step in the biosynthesis of diphthamide.

The histidine residue at position 715 of elongation factor 2 (EF-2) is posttranslationally modified in a series of enzymatic reactions to 2-[3-carboxyamido-3-(trimethylammonio)-propyl]histidine, which has been given the trivial name diphthamide. The diphthamide residue of EF-2 is the target site for ADP ribosylation by diphtheria toxin and Pseudomonas exotoxin A. ADP-ribosylated EF-2 does not function in protein synthesis. EF-2 that has not been posttranslationally modified at histidine 715 is resistant to ADP ribosylation by these toxins. In this report we show that a G-to-A transition in the first position of codon 717 of the EF-2 gene results in substitution of arginine for glycine and prevents addition of the side chain of diphthamide to histidine 715 of EF-2. EF-2 produced by the mutant gene is fully functional in protein synthesis.