Evidence map›Paper›PMID 31932721›Full record

ArticleNature chemical biology2020

Reprogramming fatty acyl specificity of lipid kinases via C1 domain engineering.

Timothy B Ware, Caroline E Franks, Mitchell E Granade, Mingxing Zhang, Kee-Beom Kim, Kwon-Sik Park, Andreas Gahlmann, Thurl E Harris, Ku-Lung Hsu

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.9field-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

21 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. bioRxiv : the preprint server for biology · 2026
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  15. Elusive structure of mammalian DGKs.Advances in biological regulation · 2022
    Review
  16. Review
  17. Article
  18. Review
  19. 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

9 authors at 2 institutions in 1 country.

Timothy B WareDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-2870-7812
Caroline E FranksDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Mitchell E GranadeDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Mingxing ZhangDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Kee-Beom KimDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Kwon-Sik ParkDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Andreas GahlmannDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Thurl E HarrisDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Ku-Lung HsuDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA. kenhsu@virginia.edu.ORCID http://orcid.org/0000-0001-5620-3972
University of Virginia · USUniversity of Virginia Health System · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
TRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2M
BIOTECHNOLOGY TRAINING PROGRAMT32GM008715 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LAURIE, GORDON WILLIAM · 2000 to 2019
$6.6M
Endocannabinoid Biosynthesis in Inflammation and PainR01DA043571 · NIDA · UNIVERSITY OF VIRGINIA · PI Ku-Lung Hsu · 2017 to 2026
$3.5M
Role of Oxidized neutral lipids in adipocyte functionR01DK101946 · NIDDK · UNIVERSITY OF VIRGINIA · PI HARRIS, THURL E. · 2014 to 2018
$1.7M
Functional Characterization of Diacylglycerol Lipases in Mammalian PhysiologyR00DA035864 · NIDA · UNIVERSITY OF VIRGINIA · PI HSU, KU-LUNG · 2015 to 2017
$744k
Zeiss 780 NLO High Sensitivity Multiphoton Microscopy SystemS10OD016446 · OD · UNIVERSITY OF VIRGINIA · PI PERIASAMY, AMMASI · 2013 to 2013
$600k
Functional Characterization of Diacylglycerol Lipases in Mammalian PhysiologyK99DA035864 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI HSU, KU-LUNG · 2014 to 2014
$128k
NCI NIH HHS P30 CA044579NIDA NIH HHS K99 DA035864NIDA NIH HHS R00 DA035864NIDA NIH HHS R01 DA043571NIDDK NIH HHS R01 DK101946NIGMS NIH HHS T32 GM007055NIGMS NIH HHS T32 GM008715NIH HHS S10 OD016446
6 · The paper itself

Abstract

C1 domains are lipid-binding modules that regulate membrane activation of kinases, nucleotide exchange factors and other C1-containing proteins to trigger signal transduction. Despite annotation of typical C1 domains as diacylglycerol (DAG) and phorbol ester sensors, the function of atypical counterparts remains ill-defined. Here, we assign a key role for atypical C1 domains in mediating DAG fatty acyl specificity of diacylglycerol kinases (DGKs) in live cells. Activity-based proteomics mapped C1 probe binding as a principal differentiator of type 1 DGK active sites that combined with global metabolomics revealed a role for C1s in lipid substrate recognition. Protein engineering by C1 domain swapping demonstrated that exchange of typical and atypical C1s is functionally tolerated and can directly program DAG fatty acyl specificity of type 1 DGKs. Collectively, we describe a protein engineering strategy for studying metabolic specificity of lipid kinases to assign a role for atypical C1 domains in cell metabolism.

Indexed as

AnimalsCatalytic DomainChromatography, LiquidDiacylglycerol KinaseGene Expression Regulation, EnzymologicHEK293 CellsHumansMetabolomicsMolecular ProbesPhosphatidic AcidsProtein DomainsProtein EngineeringProteomicsRatsSubstrate SpecificityTandem Mass SpectrometryDGKE protein, humanDiacylglycerol KinaseMolecular ProbesPhosphatidic Acids

Identifiers

PMID31932721
PMCPMC7117826
OpenAlexW2999534608

What OpenQuestion holds

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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.