InterPro domain: IPR007872

This entry represents the DPH-type metal binding domain consists of a three-stranded beta-sandwich with one sheet comprising two parallel strands: (i) beta1 and (ii) beta6 and one anti-parallel strand: beta5. The second sheet in the beta-sandwich is comprised of strands beta2, beta3, and beta4 running anti-parallel to each other. The two beta-sheets are separated by a short stretch alpha-helix.It can be found in proteins such as DPH3 and DPH4. This domain is also found associated with N-terminal domain of heat shock protein DnaJ IPR001623 domain [ 1 , 2 , 3 ].

Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaea to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyse the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death [ 4 ]. The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region, which encode a putative zinc finger, the DPH-type or CSL-type (after the the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity [ 5 , 6 , 7 , 7 , 8 , 8 ].

1. Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module. Biochemistry 44, 8801-9
2. Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4. J. Biol. Chem. 287, 13194-205
3. Structure of the Kti11/Kti13 heterodimer and its double role in modifications of tRNA and eukaryotic elongation factor 2. Structure 23, 149-160
4. Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century. Toxicon 39, 1793-803
5. Retroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins. Mol. Cell 12, 603-13
6. 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, 9487-97
7. Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain. J. Mol. Biol. 375, 301-15