Reaction: 4 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = 4 S-adenosyl-L-homocysteine + diphthine methyl ester-[translation elongation factor 2]
For diagram of reaction click here.
Glossary: diphthine methyl ester = 2-[(3S)-4-methoxy-4-oxo-3-(trimethylammonio)butyl]-L-histidine
Other name(s): S-adenosyl-L-methionine:elongation factor 2 methyltransferase (ambiguous); diphthine methyltransferase (ambiguous); Dph5 (ambiguous)
Systematic name: S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine methyl ester-[translation elongation factor 2]-forming)
Comments: This eukaryotic enzyme is part of the biosynthetic pathway of diphthamide. Different from the archaeal enzyme, which performs only 3 methylations, producing diphthine (cf. EC 220.127.116.11). The relevant histidine of elongation factor 2 is His715 in mammals and His699 in yeast. The order of the 4 methylations is not known.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
1. Chen, J.-Y.C. and Bodley, J.W. Biosynthesis of diphthamide in Saccharomyces cerevisiae. Partial purification and characterization of a specific S-adenosylmethionine:elongation factor 2 methyltransferase. J. Biol. Chem. 263 (1988) 11692-11696. [PMID: 3042777]
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. Lin, Z., Su, X., Chen, W., Ci, B., Zhang, S. and Lin, H. Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis. J. Am. Chem. Soc. 136 (2014) 6179-6182. [PMID: 24739148]