Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.

Koray Ütkür, Klaus Mayer, Shihui Liu, Ulrich Brinkmann, Raffael Schaffrath

Open access · goldAbstract read

In one paragraph

Article in Biomolecules, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Koray ÜtkürInstitut für Biologie, Fachgebiet Mikrobiologie, Universität Kassel, 34132 Kassel, Germany.

Klaus MayerRoche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Munich, 82377 Penzberg, Germany.ORCID 0000-0001-9853-2299

Shihui LiuDivision of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Ulrich BrinkmannRoche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Munich, 82377 Penzberg, Germany.ORCID 0000-0002-5558-0212

Raffael SchaffrathInstitut für Biologie, Fachgebiet Mikrobiologie, Universität Kassel, 34132 Kassel, Germany.ORCID 0000-0001-9484-5247

Roche Pharma AG (Germany) · DEUniversity of Kassel · DEUniversity of Pittsburgh · US

Funding

Deutsche Forschungsgemeinschaft Priority Program 1927 'Iron-Sulfur for Life' SCHA750/21-1Zentraler Forschungsfonds (ZFF), Universität Kassel, Germany Pilotgrant 'Diphthamide' 2887

6 · The paper itself

Abstract

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif is found next to another ill-defined cysteine that we show is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCMs) suggests a candidate Fe-S cluster ligand role. Hence, we generated, by site-directed

Indexed as

Amino Acid MotifsCysteineRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCarbon-Sulfur LyasesHistidineMutagenesis, Site-DirectedProtein MultimerizationCarbon-Sulfur LyasesCysteinediphthamideHistidineKTI11 protein, S cerevisiaeRepressor ProteinsSaccharomyces cerevisiae ProteinsADP-ribosylationcysteine ligandsdiphthamide modificationDph1•Dph2eEF2iron sulfur clusterradical SAM enzymeSaccharomyces cerevisiae

Identifiers

PMID38672486

DOI10.3390/biom14040470

PMCPMC11048331

OpenAlexW4394764816

What OpenQuestion holds

Textmetadata

LicenceCC BY

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.