Diphthamide is a unique post-translationallymodified 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 []. 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 [, , , , , ].This entry represents the DPH-type metal binding domain consists of a three-stranded β-sandwich with one sheet comprising two parallel strands: (i) β1 and (ii) β6 and one antiparallel strand: β5. The second sheet in the β-sandwich is comprised of strands β2, β3, and β4 running anti-parallel to each other. The two β-sheets are separated by a short stretch α-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 domain [, , ].
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 []. 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 [, , , , , ].This entry includes DPH3, DPH4 and their homologues.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [, , , , ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the DPH-type metal binding domain consists of a three-stranded β-sandwich with one sheet comprising two parallel strands: (i) β1 and (ii) β6 and one antiparallel strand: β5. The second sheet in the β-sandwich is comprised of strands β2, β3, and β4 running anti-parallel to each other. The two β-sheets are separated by a short stretch α-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 domain [, , ].
