Evidence map›Paper›PMID 27001731›Full record

ArticleNature chemistry2016

Designed metalloprotein stabilizes a semiquinone radical.

Gözde Ulas, Thomas Lemmin, Yibing Wu, George T Gassner, William F DeGrado

Open access · greenAbstract read
In one paragraph

Article in Nature chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.2field-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

31 citing papers in PubMed, 97 citations in OpenAlex.

  1. Structure-activity relationships in catalytic amyloids.Journal of inorganic biochemistry · 2026
    Article
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  5. bioRxiv : the preprint server for biology · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. The stability and dynamics of computationally designed proteins.Protein engineering, design & selection : PEDS · 2022
    Review
  12. A new regime of heme-dependent aromatic oxygenase superfamily.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Article
  14. Effects of Ionic Liquids on Metalloproteins.Molecules (Basel, Switzerland) · 2021
    Review
  15. Allosteric cooperation in a de novo-designed two-domain protein.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Article
  17. Quarterly reviews of biophysics · 2020
    Review
  18. Review
  19. Article
  20. Review
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 2 institutions in 1 country.

Gözde UlasDepartment of Pharmaceutical Chemistry, University of California - San Francisco, San Francisco, California 94158, USA.
Thomas LemminDepartment of Pharmaceutical Chemistry, University of California - San Francisco, San Francisco, California 94158, USA.
Yibing WuDepartment of Pharmaceutical Chemistry, University of California - San Francisco, San Francisco, California 94158, USA.
George T GassnerDepartment of Chemistry and Biochemistry, San Francisco State University, San Francisco, California 94132, USA.
William F DeGradoDepartment of Pharmaceutical Chemistry, University of California - San Francisco, San Francisco, California 94158, USA.
University of California, San Francisco · USSan Francisco State University · US

Funding

De novo design of alpha-helical bundlesR37GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 2004 to 2013
$3.6M
DE NOVO DESIGN OF ALPHA HELICAL BUNDLESR01GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 1996 to 2016
$2.4M
Charge-Transfer Dynamics Relevant to Protein-Mediated Energy TransductionR01GM071628 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI THERIEN, MICHAEL J · 2004 to 2014
$2.3M
NIGMS NIH HHS GM071628NIGMS NIH HHS GM54616NIGMS NIH HHS R01 GM054616NIGMS NIH HHS R01 GM071628NIGMS NIH HHS R37 GM054616
6 · The paper itself

Abstract

Enzymes use binding energy to stabilize their substrates in high-energy states that are otherwise inaccessible at ambient temperature. Here we show that a de novo designed Zn(II) metalloprotein stabilizes a chemically reactive organic radical that is otherwise unstable in aqueous media. The protein binds tightly to and stabilizes the radical semiquinone form of 3,5-di-tert-butylcatechol. Solution NMR spectroscopy in conjunction with molecular dynamics simulations show that the substrate binds in the active site pocket where it is stabilized by metal-ligand interactions as well as by burial of its hydrophobic groups. Spectrochemical redox titrations show that the protein stabilized the semiquinone by reducing the electrochemical midpoint potential for its formation via the one-electron oxidation of the catechol by approximately 400 mV (9 kcal mol(-1)). Therefore, the inherent chemical properties of the radical were changed drastically by harnessing its binding energy to the metalloprotein. This model sets the basis for designed enzymes with radical cofactors to tackle challenging chemistry.

Indexed as

Amino Acid SequenceBenzoquinonesMagnetic Resonance SpectroscopyMetalloproteinsModels, TheoreticalMolecular Dynamics SimulationMolecular Sequence DataBenzoquinonesMetalloproteinssemiquinone radicals

Identifiers

PMID27001731
PMCPMC4857601
OpenAlexW2285452338

What OpenQuestion holds

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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.