Evidence map›Paper›PMID 32093838›Full record

ArticleMethods in enzymology2020

Protein kinase A in the neutron beam: Insights for catalysis from directly observing protons.

Oksana Gerlits, Kevin L Weiss, Matthew P Blakeley, Gianluigi Veglia, Susan S Taylor, Andrey Kovalevsky

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Methods in enzymology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Oksana GerlitsDepartment of Natural Sciences, Tennessee Wesleyan University, Athens, TN, United States. Electronic address: ogerlits@tnwesleyan.edu.
Kevin L WeissNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, United States.
Matthew P BlakeleyLarge Scale Structures Group, Institut Laue-Langevin, Grenoble, France.
Gianluigi VegliaDepartment of Chemistry, University of Minnesota, Minneapolis, MN, United States; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, United States.
Susan S TaylorDepartment of Chemistry and Biochemistry, University of California at San Diego, Lo Jolla, CA, United States.
Andrey KovalevskyNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN, United States. Electronic address: kovalevskyay@ornl.gov.

Funding

Lessons Learned from PKA: Assembly of Dynamic Macromolecular SwitchesR35GM130389 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUSAN S. TAYLOR · 2019 to 2026
$5.7M
Mapping Allosteric Cooperativity in Protein KinasesR01GM100310 · NIGMS · UNIVERSITY OF MINNESOTA · PI VEGLIA, GIANLUIGI · 2012 to 2019
$4.3M
Protein Kinase: Primary Structure and cAMP InteractionsR01GM019301 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1985 to 2013
$3.4M
PROTEIN KINASE: PRIMARY STRUCTURE AND CAMP INTERACTIONR37GM019301 · NIGMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI TAYLOR, SUSAN S · 1995 to 2004
$2.0M
NIGMS NIH HHS R01 GM019301NIGMS NIH HHS R01 GM100310NIGMS NIH HHS R35 GM130389NIGMS NIH HHS R37 GM019301
6 · The paper itself

Abstract

Protein kinases transmit chemical signals by phosphorylating substrate proteins, thus regulating a multitude of cellular processes. cAMP-dependent protein kinase (PKA), a prototypical enzyme for the whole kinase family, has been the focus of research for several decades, however, the details of the chemical mechanism of phosphoryl group transfer have remained unknown. We used neutron crystallography to map key proton sites and hydrogen bonding interactions in the PKA catalytic subunit (PKAc) in a product complex containing adenosine diphosphate (ADP) and the phosphorylated high affinity protein kinase substrate (pPKS) peptide. To improve neutron diffraction, we deuterated PKAc allowing us to use very small crystals. In the product complex, the phosphoryl group of pPKS is protonated whereas the catalytic Asp166 is not. H/D exchange analysis of the main-chain amides and comparison with the NMR analysis of PKAc with inhibitor peptide complex revealed exchangeable amides that may distinguish the catalytic and inhibited states.

Indexed as

Cyclic AMP-Dependent Protein KinasesProtonsCatalysisModels, MolecularNeutronsCyclic AMP-Dependent Protein KinasesProtonsEnzyme mechanismHydrogen bondNeutron crystallographyPhosphoryl transferProduct complexProtein kinase AProtonation stateProton transfer

Identifiers

PMID32093838
PMCPMC7494206

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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.