Evidence map›Paper›PMID 27474740›Full record

ArticleThe Journal of biological chemistry2016

The Effectors and Sensory Sites of Formaldehyde-responsive Regulator FrmR and Metal-sensing Variant.

Deenah Osman, Cecilia Piergentili, Junjun Chen, Lucy N Sayer, Isabel Usón, Thomas G Huggins, Nigel J Robinson, Ehmke Pohl

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

29 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  6. Review
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  9. Article
  10. The Mechanism of Tigecycline Resistance inInternational journal of molecular sciences · 2023
    Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. The requirement for cobalt in vitamin BBiochimica et biophysica acta. Molecular cell research · 2021
    Review
  18. Article
  19. Complexation of the nickel and cobalt transcriptional regulator RcnR with DNA.Acta crystallographica. Section F, Structural biology communications · 2020
    Article
  20. C1 Compound Biosensors: Design, Functional Study, and Applications.International journal of molecular sciences · 2019
    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

8 authors at 3 institutions in 3 countries.

Deenah OsmanFrom the Department of Chemistry, School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom.
Cecilia PiergentiliFrom the Department of Chemistry, School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom.
Junjun ChenProcter and Gamble, Mason Business Center, Cincinnati, Ohio 45040.
Lucy N SayerFrom the Department of Chemistry.
Isabel Usónthe Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Barcelona Science Park, 08028 Barcelona, Spain, and the Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Thomas G HugginsProcter and Gamble, Mason Business Center, Cincinnati, Ohio 45040.
Nigel J RobinsonFrom the Department of Chemistry, School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom, nigel.robinson@durham.ac.uk.
Ehmke PohlFrom the Department of Chemistry, School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom.
Durham University · GBProcter & Gamble (United States) · USInstitució Catalana de Recerca i Estudis Avançats · ES

Funding

Biotechnology and Biological Sciences Research Council BB/J017787/1Biotechnology and Biological Sciences Research Council BB/L013711/1
6 · The paper itself

Abstract

The DUF156 family of DNA-binding transcriptional regulators includes metal sensors that respond to cobalt and/or nickel (RcnR, InrS) or copper (CsoR) plus CstR, which responds to persulfide, and formaldehyde-responsive FrmR. Unexpectedly, the allosteric mechanism of FrmR from Salmonella enterica serovar Typhimurium is triggered by metals in vitro, and variant FrmR(E64H) gains responsiveness to Zn(II) and cobalt in vivo Here we establish that the allosteric mechanism of FrmR is triggered directly by formaldehyde in vitro Sensitivity to formaldehyde requires a cysteine (Cys(35) in FrmR) conserved in all DUF156 proteins. A crystal structure of metal- and formaldehyde-sensing FrmR(E64H) reveals that an FrmR-specific amino-terminal Pro(2) is proximal to Cys(35), and these residues form the deduced formaldehyde-sensing site. Evidence is presented that implies that residues spatially close to the conserved cysteine tune the sensitivities of DUF156 proteins above or below critical thresholds for different effectors, generating the semblance of specificity within cells. Relative to FrmR, RcnR is less responsive to formaldehyde in vitro, and RcnR does not sense formaldehyde in vivo, but reciprocal mutations FrmR(P2S) and RcnR(S2P), respectively, impair and enhance formaldehyde reactivity in vitro Formaldehyde detoxification by FrmA requires S-(hydroxymethyl)glutathione, yet glutathione inhibits formaldehyde detection by FrmR in vivo and in vitro Quantifying the number of FrmR molecules per cell and modeling formaldehyde modification as a function of [formaldehyde] demonstrates that FrmR reactivity is optimized such that FrmR is modified and frmRA is derepressed at lower [formaldehyde] than required to generate S-(hydroxymethyl)glutathione. Expression of FrmA is thereby coordinated with the accumulation of its substrate.

Indexed as

Allosteric RegulationBacterial ProteinsCatalytic DomainFormaldehydeGene Expression Regulation, BacterialMetalsSalmonella typhimuriumBacterial ProteinsFormaldehydeMetalsallosteric regulationcobaltEscherichia coli (E. coli)formaldehydeglutathionemetalRcnR/CsoRSalmonella entericazinc

Identifiers

PMID27474740
PMCPMC5016687
OpenAlexW2502546904

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.