Diphthine methyl ester synthase (DPH5) Antibody (FITC)

Background

DPH5 is a methyltransferase enzyme involved in the second step of diphthamide biosynthesis, facilitating the trimethylation of the amino-carboxypropyl intermediate generated by the DPH1-DPH2 complex. This modification is critical for the full maturation of diphthamide on eukaryotic elongation factor 2 (eEF2), which is required for ribosomal translocation during protein synthesis. Mutations in DPH5 disrupt the trimethylation process, leading to incomplete diphthamide synthesis and cellular resistance to diphtheria toxin. Structural studies of DPH5 have revealed highly conserved S-adenosylmethionine (SAM)-binding domains that enable its catalytic function. DPH5 is localized in the cytoplasm, where it interacts with downstream components of the diphthamide biosynthetic pathway. Expression analyses show that DPH5 is ubiquitously present in eukaryotic cells, but its levels are particularly high in tissues with active protein translation. Functional deficiencies in DPH5 result in translational inefficiencies, reduced cellular growth, and increased susceptibility to stress. Its evolutionary conservation and indispensable role in protein synthesis highlight DPH5's importance across eukaryotic organisms.