ArticleJournal of the American Chemical Society2014
Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic diphthamide biosynthesis.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 73 citations in OpenAlex.
- Beyond native reactivity: radical SAM enzymes as platforms for new-to-nature chemistry.RSC chemical biology · 2026Review
- Diphthamide synthesis is linked to the eEF2-client chaperone machinery.FEBS letters · 2025Article
- Article
- Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.Biomolecules · 2024Article
- Article
- Yeast geneMicrobial cell (Graz, Austria) · 2023Article
- DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.Disease models & mechanisms · 2023Article
- Mössbauer-based molecular-level decomposition of the Saccharomyces cerevisiae ironome, and preliminary characterization of isolated nuclei.Metallomics : integrated biometal science · 2022Article
- Translational fidelity and growth of Arabidopsis require stress-sensitive diphthamide biosynthesis.Nature communications · 2022Article
- Resolving the Multidecade-Long Mystery in MoaA Radical SAM Enzyme Reveals New Opportunities to Tackle Human Health Problems.ACS bio & med chem Au · 2022Review
- Iron-sulfur clusters as inhibitors and catalysts of viral replication.Nature chemistry · 2022Review
- The BJournal of inorganic biochemistry · 2022Article
- Eukaryotic TYW1 Is a Radical SAM Flavoenzyme.Biochemistry · 2021Article
- Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom to Transform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2.Journal of the American Chemical Society · 2021Article
- Iron in Translation: From the Beginning to the End.Microorganisms · 2021Review
- Functions and Regulation of Translation Elongation Factors.Frontiers in molecular biosciences · 2021Review
- Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.European journal of human genetics : EJHG · 2020Article
- Article
- Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma.Scientific reports · 2020Article
- The asymmetric function of Dph1-Dph2 heterodimer in diphthamide biosynthesis.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
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8 authors at 1 institution in 1 country.
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Abstract
Diphthamide, the target of diphtheria toxin, is a unique posttranslational modification on translation elongation factor 2 (EF2) in archaea and eukaryotes. The biosynthesis of diphthamide was proposed to involve three steps. The first step is the transfer of the 3-amino-3-carboxypropyl group from S-adenosyl-l-methionine (SAM) to the histidine residue of EF2, forming a C-C bond. Previous genetic studies showed this step requires four proteins in eukaryotes, Dph1-Dph4. However, the exact molecular functions for the four proteins are unknown. Previous study showed that Pyrococcus horikoshii Dph2 (PhDph2), a novel iron-sulfur cluster-containing enzyme, forms a homodimer and is sufficient for the first step of diphthamide biosynthesis in vitro. Here we demonstrate by in vitro reconstitution that yeast Dph1 and Dph2 form a complex (Dph1-Dph2) that is equivalent to the homodimer of PhDph2 and is sufficient to catalyze the first step in vitro in the presence of dithionite as the reductant. We further demonstrate that yeast Dph3 (also known as KTI11), a CSL-type zinc finger protein, can bind iron and in the reduced state can serve as an electron donor to reduce the Fe-S cluster in Dph1-Dph2. Our study thus firmly establishes the functions for three of the proteins involved in eukaryotic diphthamide biosynthesis. For most radical SAM enzymes in bacteria, flavodoxins and flavodoxin reductases are believed to serve as electron donors for the Fe-S clusters. The finding that Dph3 is an electron donor for the Fe-S clusters in Dph1-Dph2 is thus interesting and opens up new avenues of research on electron transfer to Fe-S proteins in eukaryotic cells.
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