Evidence map›Paper›PMID 24077226›Full record

ArticleNature structural & molecular biology2013

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Gira Bhabha, Damian C Ekiert, Madeleine Jennewein, Christian M Zmasek, Lisa M Tuttle, Gerard Kroon, H Jane Dyson, Adam Godzik, Ian A Wilson, Peter E Wright

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

112 citing papers in PubMed, 183 citations in OpenAlex.

  1. Article
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  9. Transitioning enzyme catalysis towards photocatalysis.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025
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  20. Article

52 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Gira Bhabha1] Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA. [2] Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California, USA. [3].
Damian C Ekiert
Madeleine Jennewein
Christian M Zmasek
Lisa M Tuttle
Gerard Kroon
H Jane Dyson
Adam Godzik
Ian A Wilson
Peter E Wright
Scripps Research Institute · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Structure Determination Core at SSRLU54GM094586 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2010 to 2014
$40.1M
Protein Dynamics in Dihydrofolate Reductase CatalysisR01GM075995 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WRIGHT, PETER EDWIN · 2006 to 2021
$6.1M
Development of the flexible comparative modeling toolkitR01GM101457 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI GODZIK, ADAM · 2012 to 2015
$1.5M
Development of a comprehensive system for distant homology analysisR01GM087218 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI GODZIK, ADAM · 2009 to 2010
$955k
Predoctoral Training Program in Molecular EvolutionT32GM080209 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI FINN, M.G. · 2009 to 2011
$461k
NCI NIH HHS Y1-CO-1020NIGMS NIH HHS GM080209NIGMS NIH HHS GM101457NIGMS NIH HHS GM75995NIGMS NIH HHS R01 GM075995NIGMS NIH HHS R01 GM087218NIGMS NIH HHS R01 GM101457NIGMS NIH HHS T32 GM080209NIGMS NIH HHS U54 GM094586NIGMS NIH HHS Y1-GM-1104
6 · The paper itself

Abstract

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment.

Indexed as

Evolution, MolecularAmino Acid SequenceCrystallography, X-RayEscherichia coliGenetic Complementation TestGenetic DriftHumansModels, MolecularMolecular Dynamics SimulationMolecular Sequence DataMutationProtein ConformationSelection, GeneticSequence AlignmentTetrahydrofolate DehydrogenaseTetrahydrofolate Dehydrogenase

Identifiers

PMID24077226
PMCPMC3823643
OpenAlexW2027780910

What OpenQuestion holds

Textmetadata
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.