Evidence map›Paper›PMID 34561442›Full record

ArticleNature communications2021

Extensive regulation of enzyme activity by phosphorylation in Escherichia coli.

Evgeniya Schastnaya, Zrinka Raguz Nakic, Christoph H Gruber, Peter Francis Doubleday, Aarti Krishnan, Nathan I Johns, Jimin Park, Harris H Wang, Uwe Sauer

Abstract read
In one paragraph

Article in Nature communications, 2021. 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
–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

21 citing papers in PubMed.

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  11. Systematic identification of allosteric effectors inProceedings of the National Academy of Sciences of the United States of America · 2025
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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.

Evgeniya SchastnayaInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Zrinka Raguz NakicInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-8670-699X
Christoph H GruberInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-3770-8729
Peter Francis DoubledayInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-1784-1282
Aarti KrishnanInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Nathan I JohnsDepartment of Systems Biology, Columbia University, New York, NY, USA.
Jimin ParkDepartment of Systems Biology, Columbia University, New York, NY, USA.
Harris H WangDepartment of Systems Biology, Columbia University, New York, NY, USA.
Uwe SauerInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. sauer@imsb.biol.ethz.ch.

Funding

Micron-scale Spatial Metagenomic Mapping of Microbial Biogeography in the Gastrointestinal TractR01AI132403 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Harris H Wang · 2017 to 2026
$6.0M
Discovery of immunomodulatory gut microbes with MAGICR21AI146817 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IVANOV, IVAYLO IVANOV · 2019 to 2020
$437k
NIAID NIH HHS R01 AI132403NIAID NIH HHS R21 AI146817
6 · The paper itself

Abstract

Protein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo.

Indexed as

Protein Processing, Post-TranslationalBinding SitesEnzymesEscherichia coliEscherichia coli ProteinsMass SpectrometryMetabolomicsMutationPhosphorylationProteomeProteomicsSerineThreonineTyrosineEnzymesEscherichia coli ProteinsProteomeSerineThreonineTyrosine

Identifiers

PMID34561442
PMCPMC8463566

What OpenQuestion holds

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LicenceCC BY
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.