Reaction: ATP + diphthine-[translation elongation factor 2] + NH3 = AMP + diphosphate + diphthamide-[translation elongation factor 2]
For diagram of reaction click here.
Glossary: translation elongation factor 2 = EF2 = eEF2
diphthine = 2-[(3S)-3-carboxy-3-(trimethylammonio)propyl]-L-histidine
Other name(s): diphthamide synthase; diphthamide synthetase; DPH6 (gene name); ATPBD4 (gene name)
Systematic name: diphthine-[translation elongation factor 2]:ammonia ligase (AMP-forming)
Comments: This amidase catalyses the last step in the conversion of an L-histidine residue in the translation elongation factor EF2 to diphthamide. This factor is found in all archaea and eukaryota, but not in eubacteria, and is the target of bacterial toxins such as the diphtheria toxin and the Pseudomonas exotoxin A (see EC 220.127.116.11, NAD+diphthamide ADP-ribosyltransferase). The substrate of the enzyme, diphthine, is produced by EC 18.104.22.168, diphthine synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 114514-33-9
1. Moehring, T.J. and Moehring, J.M. Mutant cultured cells used to study the synthesis of diphthamide. UCLA Symp. Mol. Cell. Biol. New Ser. 45 (1987) 53-63.
2. Moehring, J.M. and Moehring, T.J. The post-translational trimethylation of diphthamide studied in vitro. J. Biol. Chem. 263 (1988) 3840-3844. [PMID: 3346227]
3. Su, X., Lin, Z., Chen, W., Jiang, H., Zhang, S. and Lin, H. Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc. Natl. Acad. Sci. USA 109 (2012) 19983-19987. [PMID: 23169644]