Reaction: S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2] = S-methyl-5-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
For diagram of reaction click here.
Other name(s): Dph2
Systematic name: S-adenosyl-L-methionine:L-histidine-[translation elongation factor 2] 2-[(3S)-3-amino-3-carboxypropyl]transferase
Comments: A [4Fe-4S] enzyme that modifies a histidine residue of the translation elongation factor 2 (EF2) via a 3-amino-3-carboxypropyl radical. The enzyme is present in archae and eukaryotes but not in eubacteria. The enzyme is a member of the ÕAdoMet radicalÕ (radical SAM) family and generates the 3-amino-3-carboxypropyl radical by an uncanonical clevage of S-adenosyl-L-methionine. The relevant histidine of EF2 is His715 in mammals, His699 in yeast and His600 in Pyrococcus horikoshii. Part of diphthamide biosynthesis.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Liu, S., Milne, G.T., Kuremsky, J.G., Fink, G.R. and Leppla, S.H. Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Mol. Cell Biol. 24 (2004) 9487-9497. [PMID: 15485916]
2. Zhang, Y., Zhu, X., Torelli, A.T., Lee, M., Dzikovski, B., Koralewski, R.M., Wang, E., Freed, J., Krebs, C., Ealick, S.E. and Lin, H. Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme. Nature 465 (2010) 891-896. [PMID: 20559380]
3. Zhu, X., Dzikovski, B., Su, X., Torelli, A.T., Zhang, Y., Ealick, S.E., Freed, J.H. and Lin, H. Mechanistic understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] enzyme required for diphthamide biosynthesis. Mol Biosyst 7 (2011) 74-81. [PMID: 20931132]
4. Dong, M., Horitani, M., Dzikovski, B., Pandelia, M.E., Krebs, C., Freed, J.H., Hoffman, B.M. and Lin, H. Organometallic complex formed by an unconventional radical S-adenosylmethionine enzyme. J. Am. Chem. Soc. 138 (2016) 9755Ð9758. [PMID: 27465315]