Required for the first step of diphthamide biosynthesis, the transfer of 3-amino-3-carboxypropyl from S-adenosyl-L-methionine to a histidine residue. Diphthamide is a post-translational modification of histidine which occurs in elongation factor 2 (By similarity). Protein modification; peptidyl-diphthamide biosynthesis. The DPH-type metal-binding (MB) domain can bind either zinc or iron ions. Sensitive to methyl methanesulfonate (MMS, causes DNA breaks) and hydroxyurea (HU, ribonucleotide reductase inhibitor). Belongs to the DPH4 family.