Evidence map›Paper›PMID 28166210›Full record

ArticleNature chemical biology2017

A water-mediated allosteric network governs activation of Aurora kinase A.

Soreen Cyphers, Emily F Ruff, Julie M Behr, John D Chodera, Nicholas M Levinson

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024
    Review
  6. Review
  7. Article
  8. A biophysical framework for double-drugging kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. Article
  11. A biophysical framework for double-drugging kinases.bioRxiv : the preprint server for biology · 2023
    Article
  12. Review
  13. Protein kinase C: release from quarantine by mTORC2.Trends in biochemical sciences · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021
    Review
  19. Review
  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

5 authors at 2 institutions in 1 country.

Soreen CyphersDepartment of Pharmacology, University of Minnesota, Twin Cities, Minneapolis, Minnesota, USA.
Emily F RuffDepartment of Pharmacology, University of Minnesota, Twin Cities, Minneapolis, Minnesota, USA.
Julie M BehrComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
John D ChoderaComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0003-0542-119X
Nicholas M LevinsonDepartment of Pharmacology, University of Minnesota, Twin Cities, Minneapolis, Minnesota, USA.
University of Minnesota · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Kinome-Wide Spectroscopic Study of Drug Binding Site ElectrostaticsR00GM102288 · NIGMS · UNIVERSITY OF MINNESOTA · PI LEVINSON, NICHOLAS MARK · 2015 to 2017
$745k
Kinome-Wide Spectroscopic Study of Drug Binding Site ElectrostaticsK99GM102288 · NIGMS · STANFORD UNIVERSITY · PI LEVINSON, NICHOLAS MARK · 2012 to 2013
$180k
NCI NIH HHS P30 CA008748NIGMS NIH HHS K99 GM102288NIGMS NIH HHS R00 GM102288
6 · The paper itself

Abstract

The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift toward the active DFG-in state. Förster resonance energy transfer experiments show that the activation loop undergoes a nanometer-scale movement that is tightly coupled to the DFG equilibrium. Tpx2 further activates AurA by stabilizing a water-mediated allosteric network that links the C-helix to the active site through an unusual polar residue in the regulatory spine. The polar spine residue and water network of AurA are essential for phosphorylation-driven activation, but an alternative form of the water network found in related kinases can support Tpx2-driven activation, suggesting that variations in the water-mediated hydrogen bond network mediate regulatory diversification in protein kinases.

Indexed as

Allosteric RegulationAurora Kinase AEnzyme ActivationHumansModels, MolecularWaterAURKA protein, humanAurora Kinase AWater

Identifiers

PMID28166210
PMCPMC5388450
OpenAlexW2587432179

What OpenQuestion holds

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Registered trials

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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.