Evidence map›Paper›PMID 29901984›Full record

ArticleBiochemistry2018

Modulating Enzyme Activity by Altering Protein Dynamics with Solvent.

Michael R Duff, Jose M Borreguero, Matthew J Cuneo, Arvind Ramanathan, Junhong He, Ganesh Kamath, S Chakra Chennubhotla, Flora Meilleur, Elizabeth E Howell, Kenneth W Herwig and 2 more

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Asymmetric Dynamics Between the Protomers of the σ2 Receptor Homodimer.Journal of chemical information and modeling · 2025
    Article
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  10. Modulating Enzyme FunctionFrontiers in molecular biosciences · 2021
    Article
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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

12 authors at 3 institutions in 1 country.

Michael R DuffBiochemistry & Cellular and Molecular Biology Department , University of Tennessee , Knoxville , Tennessee , United States.
Jose M BorregueroNeutron Data Analysis and Visualization Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Matthew J CuneoBiology and Soft Matter Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Arvind RamanathanComputer Science and Engineering Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Junhong HeNeutron Technologies Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Ganesh KamathComputer Science and Engineering Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
S Chakra ChennubhotlaDepartment of Computational and Systems Biology , University of Pittsburgh , Pittsburgh , Pennsylvania , United States.
Flora MeilleurBiology and Soft Matter Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Elizabeth E HowellBiochemistry & Cellular and Molecular Biology Department , University of Tennessee , Knoxville , Tennessee , United States.ORCID 0000-0001-6157-433X
Kenneth W HerwigNeutron Technologies Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Dean A A MylesBiology and Soft Matter Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee , United States.
Pratul K AgarwalBiochemistry & Cellular and Molecular Biology Department , University of Tennessee , Knoxville , Tennessee , United States.ORCID 0000-0002-3848-9492
Oak Ridge National Laboratory · USUniversity of Tennessee at Knoxville · USUniversity of Pittsburgh · US

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
Osmotic Pressure and Crowding Effects on Folate Mediated One Carbon MetabolismR15GM110669 · NIGMS · UNIVERSITY OF TENNESSEE KNOXVILLE · PI HOWELL, ELIZABETH E · 2014 to 2014
$323k
NIGMS NIH HHS R01 GM105978NIGMS NIH HHS R15 GM110669
6 · The paper itself

Abstract

Optimal enzyme activity depends on a number of factors, including structure and dynamics. The role of enzyme structure is well recognized; however, the linkage between protein dynamics and enzyme activity has given rise to a contentious debate. We have developed an approach that uses an aqueous mixture of organic solvent to control the functionally relevant enzyme dynamics (without changing the structure), which in turn modulates the enzyme activity. Using this approach, we predicted that the hydride transfer reaction catalyzed by the enzyme dihydrofolate reductase (DHFR) from Escherichia coli in aqueous mixtures of isopropanol (IPA) with water will decrease by ∼3 fold at 20% (v/v) IPA concentration. Stopped-flow kinetic measurements find that the pH-independent k

Indexed as

2-PropanolCrystallography, X-RayEnzyme ActivationEscherichia coliKineticsMolecular Dynamics SimulationProtein ConformationSolventsStatic ElectricityTetrahydrofolate DehydrogenaseViscosityWater2-PropanolSolventsTetrahydrofolate DehydrogenaseWater

Identifiers

PMID29901984
PMCPMC6172137
OpenAlexW2807983615

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.