Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:15485916, PubMed:24422557, PubMed:27694803, PubMed:31463593, PubMed:34154323). In association with DPH2, transfers a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising KTI11/DPH3 and a NADH-dependent reductase, predominantly CBR1 (PubMed:15485916, PubMed:31463593, PubMed:34154323, PubMed:24422557, PubMed:27694803). L-histidyl-[translation elongation factor 2] + S-adenosyl-L-methionine = 2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation elongation factor 2] + H(+) + S-methyl-5'-thioadenosine Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. Protein modification; peptidyl-diphthamide biosynthesis. Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, KTI11/DPH3 and a NADH-dependent reductase, predominantly CBR1 (PubMed:15485916, PubMed:18627462, PubMed:23645155, PubMed:24422557, PubMed:27694803, PubMed:31463593). Interacts with DPH2; the interaction is direct (PubMed:15485916, PubMed:23645155, PubMed:31463593). Interacts with KTI11/DPH3 (PubMed:12940988, PubMed:18627462, PubMed:23645155, PubMed:27694803). Increases translational -1 frameshifting (PubMed:18627462). Abolishes the formation of the 2-(3-amino-3-carboxypropyl)histidine synthase complex (PubMed:18627462). Resistance to sordarin and zymocin (PubMed:18627462). Present with 2526 molecules/cell in log phase SD medium. Belongs to the DPH1/DPH2 family. DPH1 subfamily.