Evidence map›Paper›PMID 31040324›Full record

ArticleScientific reports2019

The Structural Dynamics of Engineered β-Lactamases Vary Broadly on Three Timescales yet Sustain Native Function.

Sophie M C Gobeil, Maximillian C C J C Ebert, Jaeok Park, Donald Gagné, Nicolas Doucet, Albert M Berghuis, Jürgen Pleiss, Joelle N Pelletier

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Editorial: Molecular evolution: You learn from your mistakes.Frontiers in molecular biosciences · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. A mechanistic view of enzyme evolution.Protein science : a publication of the Protein Society · 2020
    Review
  14. Article
  15. 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

8 authors at 4 institutions in 2 countries.

Sophie M C GobeilDépartement de biochimie and Center for Green Chemistry and Catalysis (CGCC), Université de Montréal, Montréal, QC, H3T 1J4, Canada.ORCID http://orcid.org/0000-0002-0057-2477
Maximillian C C J C EbertDépartement de biochimie and Center for Green Chemistry and Catalysis (CGCC), Université de Montréal, Montréal, QC, H3T 1J4, Canada.ORCID http://orcid.org/0000-0002-8055-8404
Jaeok ParkPROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, G1V 0A6, Canada.
Donald GagnéPROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, G1V 0A6, Canada.
Nicolas DoucetPROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, G1V 0A6, Canada.ORCID http://orcid.org/0000-0002-1952-9380
Albert M BerghuisPROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, G1V 0A6, Canada.
Jürgen PleissInstitute of Biochemistry and Technical Biochemistry, University of Stuttgart, Stuttgart, 70569, Germany.
Joelle N PelletierDépartement de biochimie and Center for Green Chemistry and Catalysis (CGCC), Université de Montréal, Montréal, QC, H3T 1J4, Canada. joelle.pelletier@umontreal.ca.
Centre in Green Chemistry and Catalysis · CAInstitut National de la Recherche Scientifique · CAPROTEO · CAUniversity of Stuttgart · DE

Funding

Conformational sub-states in enzyme catalysis: Applications to ribonucleaseR01GM105978 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AGARWAL, PRATUL K, CHENNUBHOTLA, SRINIVAS CHAKRA · 2014 to 2018
$2.8M
NIGMS NIH HHS R01 GM105978U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM105978
6 · The paper itself

Abstract

Understanding the principles of protein dynamics will help guide engineering of protein function: altering protein motions may be a barrier to success or may be an enabling tool for protein engineering. The impact of dynamics on protein function is typically reported over a fraction of the full scope of motional timescales. If motional patterns vary significantly at different timescales, then only by monitoring motions broadly will we understand the impact of protein dynamics on engineering functional proteins. Using an integrative approach combining experimental and in silico methodologies, we elucidate protein dynamics over the entire span of fast to slow timescales (ps to ms) for a laboratory-engineered system composed of five interrelated β-lactamases: two natural homologs and three laboratory-recombined variants. Fast (ps-ns) and intermediate (ns-µs) dynamics were mostly conserved. However, slow motions (µs-ms) were few and conserved in the natural homologs yet were numerous and widely dispersed in their recombinants. Nonetheless, modified slow dynamics were functionally tolerated. Crystallographic B-factors from high-resolution X-ray structures were partly predictive of the conserved motions but not of the new slow motions captured in our solution studies. Our inspection of protein dynamics over a continuous range of timescales vividly illustrates the complexity of dynamic impacts of protein engineering as well as the functional tolerance of an engineered enzyme system to new slow motions.

Indexed as

Models, MolecularProtein ConformationProtein Engineeringbeta-LactamasesBinding SitesCrystallography, X-RayKineticsNuclear Magnetic Resonance, BiomolecularProtein Bindingbeta-Lactamases

Identifiers

PMID31040324
PMCPMC6491436
OpenAlexW2943354123

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.