DPH2 transfers a 3-amino-3-carboxypropyl group from AdoMet to residue 715 of nascent EEF2

Stable Identifier
Reaction [transition]
Homo sapiens
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The diphthamide biosynthesis protein 2 (DPH2) subunit of the cytosolic DPH1:DPH2:DPH3 complex catalyzes the transfer of a 3-amino-3-carboxypropyl group from S-adenosylmethionine (AdoMet) to residue 715 of nascent elongation factor 2 (EEF2), forming aminocarboxypropyl EEF2 and S-methylthioadenosine (MTAD). The association of DPH1, 2, and 3 to form a complex is inferred from studies of the homologous yeast proteins (Abdel-Fattah et al. 2013; Bar et al. 2008) and more limited studies of interactions among mouse and human ones (Liu et al. 2004). The identification of DPH2 as the catalytically active subunit of the DPH1:DPH2:DPH3 complex is inferred from the properties of the homologous Pyrococcus horikoshii protein (Zhang et al. 2010). DPH4 (DNAJC24) is needed for the reaction to occur but its exact role is unknown (Liu et al. 2004; Su et al. 2013). DPH3 is an electron donor for DPH1-DPH2 in the first step of diphthamide biosynthesis (Dong et al. 2014).
Literature References
PubMed ID Title Journal Year
24422557 Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic diphthamide biosynthesis

Dando, EE, Du, J, Su, X, Freed, JH, Lin, H, Dong, M, Dzikovski, B, Zhu, X

J. Am. Chem. Soc. 2014
23645155 Insights into diphthamide, key diphtheria toxin effector

Uthman, S, Schaffrath, R, Stark, MJ, Scheidt, V, Abdel-Fattah, W

Toxins (Basel) 2013
23971743 The biosynthesis and biological function of diphthamide

Su, X, Lin, Z, Lin, H

Crit. Rev. Biochem. Mol. Biol. 2013
20559380 Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme

Lee, M, Torelli, AT, Freed, J, Koralewski, RM, Wang, E, Zhang, Y, Krebs, C, Lin, H, Ealick, SE, Dzikovski, B, Zhu, X

Nature 2010
18627462 A versatile partner of eukaryotic protein complexes that is involved in multiple biological processes: Kti11/Dph3

Schaffrath, R, Stark, MJ, Liu, S, Zabel, R, Bär, C

Mol. Microbiol. 2008
15485916 Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2

Leppla, SH, Liu, S, Kuremsky, JG, Fink, GR, Milne, GT

Mol. Cell. Biol. 2004
Catalyst Activity

2-(3-amino-3-carboxypropyl)histidine synthase activity of DPH1:DPH2:DPH3 [cytosol]

This event is regulated
Positively by
Orthologous Events
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