Evidence map›Paper›PMID 26258763›Full record

ArticleNature chemical biology2015

An excess of catalytically required motions inhibits the scavenger decapping enzyme.

Ancilla Neu, Ursula Neu, Anna-Lisa Fuchs, Benjamin Schlager, Remco Sprangers

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023
    Article
  4. Article
  5. Assessing the applicability ofJournal of biomolecular NMR · 2023
    Article
  6. Article
  7. Article
  8. Molecular basis of the selective processing of short mRNA substrates by the DcpS mRNA decapping enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  9. Article
  10. Article
  11. Review
  12. Role of conformational dynamics in the evolution of novel enzyme function.Chemical communications (Cambridge, England) · 2018
    Review
  13. Article
  14. Article
  15. Changes in conformational equilibria regulate the activity of the Dcp2 decapping enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Ancilla NeuMax Planck Institute for Developmental Biology, Tübingen, Germany.
Ursula NeuInterfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Anna-Lisa FuchsMax Planck Institute for Developmental Biology, Tübingen, Germany.
Benjamin SchlagerMax Planck Institute for Developmental Biology, Tübingen, Germany.
Remco SprangersMax Planck Institute for Developmental Biology, Tübingen, Germany.
Max Planck Institute for Developmental Biology · DEMax Planck Society · DEUniversity of Tübingen · DE

Funding

European Research Council 616052
6 · The paper itself

Abstract

The scavenger decapping enzyme hydrolyzes the protective 5' cap structure on short mRNA fragments that are generated from the exosomal degradation of mRNAs. From static crystal structures and NMR data, it is apparent that the dimeric enzyme has to undergo large structural changes to bind its substrate in a catalytically competent conformation. Here we studied the yeast enzyme and showed that the associated opening and closing motions can be orders of magnitude faster than the catalytic turnover rate. This excess of motion is induced by the binding of a second ligand to the enzyme, which occurs at high substrate concentrations. We designed a mutant that disrupted the allosteric pathway that links the second binding event to the dynamics and showed that this mutant enzyme is hyperactive. Our data reveal a unique mechanism of substrate inhibition in which motions that are required for catalytic activity also inhibit efficient turnover when they are present in excess.

Indexed as

Feedback, PhysiologicalAllosteric RegulationAllosteric SiteBiocatalysisCatalytic DomainCrystallography, X-RayEndoribonucleasesEscherichia coliGene ExpressionKineticsMolecular Dynamics SimulationN-Glycosyl HydrolasesProtein BindingProtein MultimerizationRecombinant ProteinsRNA, MessengerDCS1 protein, S cerevisiaeEndoribonucleasesmRNA decapping enzymesN-Glycosyl HydrolasesRecombinant ProteinsRNA, MessengerSaccharomyces cerevisiae Proteins

Identifiers

PMID26258763
PMCPMC4544744
OpenAlexW1181555117

What OpenQuestion holds

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LicenceTDM
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.