Evidence map›Paper›PMID 36892429›Full record

ReviewFEBS letters2023

An NMR portrait of functional and dysfunctional allosteric cooperativity in cAMP-dependent protein kinase A.

Cristina Olivieri, Caitlin Walker, Manu Veliparambil Subrahmanian, Fernando Porcelli, Susan S Taylor, David A Bernlohr, Gianluigi Veglia

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in FEBS letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Allosteric Protein Chemical Shift Perturbations are Ubiquitous.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Local and distal changes in dynamics are caused by an L205R Cushing's syndrome mutant in PRKACA.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Review
  5. Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024
    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

7 authors at 3 institutions in 2 countries.

Cristina OlivieriDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-6957-6743
Caitlin WalkerDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0003-0977-8276
Manu Veliparambil SubrahmanianDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-1374-2797
Fernando PorcelliDepartment for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia, Viterbo, Italy.ORCID 0000-0003-3209-0074
Susan S TaylorDepartment of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California, USA.ORCID 0000-0002-7702-6108
David A BernlohrDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-6969-9129
Gianluigi VegliaDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-2795-6964
University of Minnesota · USUniversità degli Studi della Tuscia · ITUniversity of California San Diego · US

Funding

Mapping Allosteric Cooperativity in Protein KinasesR01GM100310 · NIGMS · UNIVERSITY OF MINNESOTA · PI VEGLIA, GIANLUIGI · 2012 to 2019
$4.3M
Structural Basis of Dilated CardiomyopathyR01HL144130 · NHLBI · UNIVERSITY OF MINNESOTA · PI VEGLIA, GIANLUIGI · 2018 to 2021
$1.5M
American Heart Association-American Stroke Association 20PRE35120253 - CAITLIN WALKERNHLBI NIH HHS R01 HL144130NIGMS NIH HHS R01 GM100310
6 · The paper itself

Abstract

The cAMP-dependent protein kinase A (PKA) is the archetypical eukaryotic kinase. The catalytic subunit (PKA-C) structure is highly conserved among the AGC-kinase family. PKA-C is a bilobal enzyme with a dynamic N-lobe, harbouring the Adenosine-5'-triphosphate (ATP) binding site and a more rigid helical C-lobe. The substrate-binding groove resides at the interface of the two lobes. A distinct feature of PKA-C is the positive binding cooperativity between nucleotide and substrate. Several PKA-C mutations lead to the development of adenocarcinomas, myxomas, and other rare forms of liver tumours. Nuclear magnetic resonance (NMR) spectroscopy shows that these mutations disrupt the allosteric communication between the two lobes, causing a drastic decrease in binding cooperativity. The loss of cooperativity correlates with changes in substrate fidelity and reduced kinase affinity for the endogenous protein kinase inhibitor (PKI). The similarity between PKI and the inhibitory sequence of the kinase regulatory subunits suggests that the overall mechanism of regulation of the kinase may be disrupted. We surmise that a reduced or obliterated cooperativity may constitute a common trait for both orthosteric and allosteric mutations of PKA-C that may lead to dysregulation and disease.

Indexed as

Cyclic AMP-Dependent Protein KinasesNucleotidesAdenosine TriphosphateAllosteric RegulationBinding SitesCatalytic DomainMagnetic Resonance SpectroscopyAdenosine TriphosphateCyclic AMP-Dependent Protein KinasesNucleotidesallosteric regulationconformational entropycooperativityNMRprotein kinases

Identifiers

PMID36892429
PMCPMC11334100
OpenAlexW4323653671

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.