Home  |  Contact
PROSITE documentation PDOC51074

DPH-type metal-binding (MB) domain profile





Description

Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaebacteria to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyze the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death [1].

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 encodes a metal-binding (MB) domain. The DHP-type or CSL-type (named after 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 [2,3,4,5,6,7].

The DPH-type MB domain consists of a three-stranded β-sandwich with one sheet comprising two parallel strands: (i) β1 and (ii) β6 and one anti-parallel 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 (see <PDB:2L6L>) [4,6,7].

The profile we developed covers the whole DPH-type MB domain.

Last update:

July 2019 / Text revised.

-------------------------------------------------------------------------------

Technical section

PROSITE method (with tools and information) covered by this documentation:

DPH_MB, PS51074; DPH-type metal-binding (MB) domain profile  (MATRIX)


References

1AuthorsCollier R.J.
TitleUnderstanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century.
SourceToxicon 39:1793-1803(2001).
PubMed ID11595641

2AuthorsLiu S. Leppla S.H.
TitleRetroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins.
SourceMol. Cell 12:603-613(2003).
PubMed ID14527407

3AuthorsLiu S. Milne G.T. Kuremsky J.G. Fink G.R. Leppla S.H.
TitleIdentification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2.
SourceMol. Cell. Biol. 24:9487-9497(2004).
PubMed ID15485916
DOI10.1128/MCB.24.21.9487-9497.2004

4AuthorsSun J. Zhang J. Wu F. Xu C. Li S. Zhao W. Wu Z. Wu J. Zhou C.-Z. Shi Y.
TitleSolution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module.
SourceBiochemistry 44:8801-8809(2005).
PubMed ID15952786
DOI10.1021/bi0504714

5AuthorsProudfoot M. Sanders S.A. Singer A. Zhang R. Brown G. Binkowski A. Xu L. Lukin J.A. Murzin A.G. Joachimiak A. Arrowsmith C.H. Edwards A.M. Savchenko A.V. Yakunin A.F.
TitleBiochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain.
SourceJ. Mol. Biol. 375:301-315(2008).
PubMed ID18021800
DOI10.1016/j.jmb.2007.10.060

6AuthorsThakur A. Chitoor B. Goswami A.V. Pareek G. Atreya H.S. D'Silva P.
TitleStructure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4.
SourceJ. Biol. Chem. 287:13194-13205(2012).
PubMed ID22367199
DOI10.1074/jbc.M112.339655

7AuthorsGlatt S. Zabel R. Vonkova I. Kumar A. Netz D.J. Pierik A.J. Rybin V. Lill R. Gavin A.-C. Balbach J. Breunig K.D. Mueller C.W.
TitleStructure of the Kti11/Kti13 heterodimer and its double role in modifications of tRNA and eukaryotic elongation factor 2.
SourceStructure 23:149-160(2015).
PubMed ID25543256
DOI10.1016/j.str.2014.11.008



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)