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PROSITE documentation PDOC51074DPH-type metal-binding (MB) domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51074
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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Collier R.J. |
| Title | Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century. | |
| Source | Toxicon 39:1793-1803(2001). | |
| PubMed ID | 11595641 |
| 2 | Authors | Liu S. Leppla S.H. |
| Title | Retroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins. | |
| Source | Mol. Cell 12:603-613(2003). | |
| PubMed ID | 14527407 |
| 3 | Authors | Liu S. Milne G.T. Kuremsky J.G. Fink G.R. Leppla S.H. |
| Title | Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. | |
| Source | Mol. Cell. Biol. 24:9487-9497(2004). | |
| PubMed ID | 15485916 | |
| DOI | 10.1128/MCB.24.21.9487-9497.2004 |
| 4 | Authors | Sun J. Zhang J. Wu F. Xu C. Li S. Zhao W. Wu Z. Wu J. Zhou C.-Z. Shi Y. |
| Title | Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module. | |
| Source | Biochemistry 44:8801-8809(2005). | |
| PubMed ID | 15952786 | |
| DOI | 10.1021/bi0504714 |
| 5 | Authors | Proudfoot 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. |
| Title | Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain. | |
| Source | J. Mol. Biol. 375:301-315(2008). | |
| PubMed ID | 18021800 | |
| DOI | 10.1016/j.jmb.2007.10.060 |
| 6 | Authors | Thakur A. Chitoor B. Goswami A.V. Pareek G. Atreya H.S. D'Silva P. |
| Title | Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4. | |
| Source | J. Biol. Chem. 287:13194-13205(2012). | |
| PubMed ID | 22367199 | |
| DOI | 10.1074/jbc.M112.339655 |
| 7 | Authors | Glatt 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. |
| Title | Structure of the Kti11/Kti13 heterodimer and its double role in modifications of tRNA and eukaryotic elongation factor 2. | |
| Source | Structure 23:149-160(2015). | |
| PubMed ID | 25543256 | |
| DOI | 10.1016/j.str.2014.11.008 |
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