Evidence map›Paper›PMID 29215013›Full record

ArticleNature communications2017

Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and sugar levels in Mycobacterium tuberculosis.

Wenhe Zhong, Liang Cui, Boon Chong Goh, Qixu Cai, Peiying Ho, Yok Hian Chionh, Meng Yuan, Abbas El Sahili, Linda A Fothergill-Gilmore, Malcolm D Walkinshaw and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

34 citing papers in PubMed, 64 citations in OpenAlex.

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  14. Analysis ofFoods (Basel, Switzerland) · 2023
    Article
  15. Article
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  17. Catalyst-based biomolecular logic gates.Catalysts (Basel, Switzerland) · 2022
    Article
  18. Article
  19. Article
  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

12 authors at 5 institutions in 4 countries.

Wenhe ZhongInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore.
Liang CuiInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore.
Boon Chong GohInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore.
Qixu CaiDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Peiying HoInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore.
Yok Hian ChionhInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore.ORCID http://orcid.org/0000-0002-4909-8382
Meng YuanInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3BF, UK.
Abbas El SahiliNTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore.
Linda A Fothergill-GilmoreInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3BF, UK.
Malcolm D WalkinshawInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3BF, UK.ORCID http://orcid.org/0000-0001-5955-9325
Julien LescarNTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore. julien@ntu.edu.sg.
Peter C DedonInfectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, 138602, Singapore. pcdedon@mit.edu.
Nanyang Technological University · SGSingapore-MIT Alliance for Research and Technology · SGUniversity of Edinburgh · GBHong Kong University of Science and Technology · HKScripps Research Institute · US

Funding

Medical Research Council G0600014Medical Research Council MC_PC_14104
6 · The paper itself

Abstract

Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism. G6P was found to bind to a previously unknown site adjacent to the canonical site for AMP. Kinetic data and structural network analysis further show that AMP and G6P work synergistically as allosteric activators. Importantly, metabolome profiling in the Mtb surrogate, Mycobacterium bovis BCG, reveals significant changes in AMP and G6P levels during nutrient deprivation, which provides insights into how a PYK OR gate would function during the stress of Mtb infection.

Indexed as

Adenosine MonophosphateAllosteric RegulationCrystallography, X-RayEnzyme AssaysGlucoseGlucose-6-PhosphateKineticsMetabolomeMetabolomicsMolecular Docking SimulationMycobacterium bovisMycobacterium tuberculosisProtein DomainsPyruvate KinaseAdenosine MonophosphateGlucoseGlucose-6-PhosphatePyruvate Kinase

Identifiers

PMID29215013
PMCPMC5719368
OpenAlexW2774928686

What OpenQuestion holds

Textmetadata
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.