Reaction: 3 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = 3 S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2] (overall reaction)
(1a) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2]
(1b) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2]
(1c) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2]
For diagram of reaction click here.
Glossary: diphthine = 2-[(3S)-3-carboxy-3-(trimethylamino)propyl]-L-histidine
Other name(s): S-adenosyl-L-methionine:elongation factor 2 methyltransferase (ambiguous); diphthine methyltransferase (ambiguous); S-adenosyl-L-methionine:2-(3-carboxy-3-aminopropyl)-L-histidine-[translation elongation factor 2] methyltransferase; Dph5 (ambiguous)
Systematic name: S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine-[translation elongation factor 2]-forming)
Comments: This archaeal enzyme produces the trimethylated product diphthine, which is converted into diphthamide by EC 6.3.1.14, diphthine—ammonia ligase. Different from the eukaryotic enzyme, which produces diphthine methyl ester (cf. EC 2.1.1.314). In the archaeon Pyrococcus horikoshii the enzyme acts on His600 of elongation factor 2.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 114514-25-9
References:
1. Zhu, X., Kim, J., Su, X. and Lin, H. Reconstitution of diphthine synthase activity in vitro. Biochemistry 49 (2010) 9649-9657. [PMID: 20873788]