Evidence map›Paper›PMID 26079622›Full record

ArticleAngewandte Chemie (International ed. in English)2015

Chemical Ligation and Isotope Labeling to Locate Dynamic Effects during Catalysis by Dihydrofolate Reductase.

Louis Y P Luk, J Javier Ruiz-Pernía, Aduragbemi S Adesina, E Joel Loveridge, Iñaki Tuñón, Vincent Moliner, Rudolf K Allemann

Open access · bronzeAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.0field-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

20 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.Chembiochem : a European journal of chemical biology · 2021
    Article
  5. Review
  6. Approaches for peptide and protein cyclisation.Organic & biomolecular chemistry · 2021
    Review
  7. Article
  8. Article
  9. Heavy Enzymes and the Rational Redesign of Protein Catalysts.Chembiochem : a European journal of chemical biology · 2019
    Article
  10. Article
  11. Article
  12. Protein Mass Effects on Formate Dehydrogenase.Journal of the American Chemical Society · 2017
    Article
  13. Protonation-Initiated Cyclization by a Class II Terpene Cyclase Assisted by Tunneling.Chembiochem : a European journal of chemical biology · 2017
    Article
  14. Quantifying the limits of transition state theory in enzymatic catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 3 institutions in 2 countries.

Louis Y P LukSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT (UK).
J Javier Ruiz-PerníaDepartament de Química Física i Analítica, Universitat Jaume I, 12071 Castelló (Spain).
Aduragbemi S AdesinaSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT (UK).
E Joel LoveridgeSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT (UK).
Iñaki TuñónDepartament de Química Física, Universitat de València, 46100 Burjassot (Spain). ignacio.tunon@uv.es.
Vincent MolinerDepartament de Química Física i Analítica, Universitat Jaume I, 12071 Castelló (Spain). moliner@uji.es.
Rudolf K AllemannSchool of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT (UK). allemannrk@cardiff.ac.uk.
Cardiff University · GBUniversitat de València · ESUniversitat Jaume I · ES

Funding

Biotechnology and Biological Sciences Research Council BB/J005266/1Biotechnology and Biological Sciences Research Council BB/L020394/1
6 · The paper itself

Abstract

Chemical ligation has been used to alter motions in specific regions of dihydrofolate reductase from E. coli and to investigate the effects of localized motional changes on enzyme catalysis. Two isotopic hybrids were prepared; one with the mobile N-terminal segment containing heavy isotopes ((2) H, (13) C, (15) N) and the remainder of the protein with natural isotopic abundance, and the other one with only the C-terminal segment isotopically labeled. Kinetic investigations indicated that isotopic substitution of the N-terminal segment affected only a physical step of catalysis, whereas the enzyme chemistry was affected by protein motions from the C-terminal segment. QM/MM studies support the idea that dynamic effects on catalysis mostly originate from the C-terminal segment. The use of isotope hybrids provides insights into the microscopic mechanism of dynamic coupling, which is difficult to obtain with other studies, and helps define the dynamic networks of intramolecular interactions central to enzyme catalysis.

Indexed as

CatalysisIsotope LabelingLigationModels, MolecularTetrahydrofolate DehydrogenaseTetrahydrofolate Dehydrogenasechemical ligationenzyme catalysisisotope effectsmicroscopic mechanismsprotein dynamics

Identifiers

PMID26079622
PMCPMC4985705
OpenAlexW2155954777

What OpenQuestion holds

Textmetadata
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.