| Type |
Details |
Score |
| Protein Domain |
| Type: |
Family |
| Description: |
This entry includes diphthamide synthesis DPH1 from eukaryotes and archaea and DPH2 from archaea.Archaeal and eukaryotic translation elongation factor 2 (EF-2) contain a unique posttranslationally modified histidine residue called diphthamide, which become the target for ADP-ribosylation by diphtheria toxin []. DPH1 catalyzes the first step of diphthamide biosynthesis and is required for the modification of EF-2 []. The human DPH1 is also known as OVCA1 (for ovarian cancer gene 1), a tumour suppressor gene that plays a crucial role in the regulation of cell proliferation, embryonic development, and tumorigenesis []. |
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| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
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•
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| Publication |
| First Author: |
Webb TR |
| Year: |
2008 |
| Journal: |
J Cell Sci |
| Title: |
Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development. |
| Volume: |
121 |
| Issue: |
Pt 19 |
| Pages: |
3140-5 |
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•
•
•
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| Publication |
| First Author: |
Dong M |
| Year: |
2014 |
| Journal: |
J Am Chem Soc |
| Title: |
Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic diphthamide biosynthesis. |
| Volume: |
136 |
| Issue: |
5 |
| Pages: |
1754-7 |
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•
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•
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| Publication |
| First Author: |
Zhang Y |
| Year: |
2010 |
| Journal: |
Nature |
| Title: |
Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme. |
| Volume: |
465 |
| Issue: |
7300 |
| Pages: |
891-6 |
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
438
 |
| Fragment?: |
false |
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•
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
275
|
| Fragment?: |
true |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. Thismodified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 [].The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 [].Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangement resemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s [].This superfamily represents the domain 2 found in diphthamide synthesis DPH1/DPH2 enzymes. |
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•
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. This modified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 [].The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 [].Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangement resemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s [].This superfamily represents the domain 1 found in diphthamide synthesis DPH1/DPH2 enzymes. |
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•
•
•
•
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. This modified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 [].The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 [].Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangementresemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s [].This superfamily represents the domain 3 found in diphthamide synthesis DPH1/DPH2 enzymes. |
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