Evidence map›Paper›PMID 26450927›Full record

ArticleBioscience reports2015

Biochemical studies on Francisella tularensis RelA in (p)ppGpp biosynthesis.

Rachael C Wilkinson, Laura E Batten, Neil J Wells, Petra C F Oyston, Peter L Roach

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Rachael C WilkinsonDepartment of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K.
Laura E BattenDepartment of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K.
Neil J WellsDepartment of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K.
Petra C F OystonInstitute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, U.K. DSTL, Porton Down, Salisbury, SP4 OJQ, U.K.
Peter L RoachDepartment of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K. Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, U.K. plr2@soton.ac.uk.
University of Southampton · GBDefence Science and Technology Laboratory · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The bacterial stringent response is induced by nutrient deprivation and is mediated by enzymes of the RSH (RelA/SpoT homologue; RelA, (p)ppGpp synthetase I; SpoT, (p)ppGpp synthetase II) superfamily that control concentrations of the 'alarmones' (p)ppGpp (guanosine penta- or tetra-phosphate). This regulatory pathway is present in the vast majority of pathogens and has been proposed as a potential anti-bacterial target. Current understanding of RelA-mediated responses is based on biochemical studies using Escherichia coli as a model. In comparison, the Francisella tularensis RelA sequence contains a truncated regulatory C-terminal region and an unusual synthetase motif (EXSD). Biochemical analysis of F. tularensis RelA showed the similarities and differences of this enzyme compared with the model RelA from Escherichia coli. Purification of the enzyme yielded a stable dimer capable of reaching concentrations of 10 mg/ml. In contrast with other enzymes from the RelA/SpoT homologue superfamily, activity assays with F. tularensis RelA demonstrate a high degree of specificity for GTP as a pyrophosphate acceptor, with no measurable turnover for GDP. Steady state kinetic analysis of F. tularensis RelA gave saturation activity curves that best fitted a sigmoidal function. This kinetic profile can result from allosteric regulation and further measurements with potential allosteric regulators demonstrated activation by ppGpp (5',3'-dibisphosphate guanosine) with an EC50 of 60±1.9 μM. Activation of F. tularensis RelA by stalled ribosomal complexes formed with ribosomes purified from E. coli MRE600 was observed, but interestingly, significantly weaker activation with ribosomes isolated from Francisella philomiragia.

Indexed as

Allosteric RegulationEscherichia coliFrancisella tularensisKineticsLigasesRibosomesguanosine 3',5'-polyphosphate synthetasesLigases3′-dibisphosphate guanosine (ppGpp)5′FrancisellakineticsRelA (p)ppGpp synthetase Istringent responsesynthetase

Identifiers

PMID26450927
PMCPMC4708007
OpenAlexW2270890522

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.