Evidence map›Paper›PMID 27851736›Full record

ArticleNature2016

An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme.

Mary Ortmayer, Pierre Lafite, Binuraj R K Menon, Tewes Tralau, Karl Fisher, Lukas Denkhaus, Nigel S Scrutton, Stephen E J Rigby, Andrew W Munro, Sam Hay and 1 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

11 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. A conserved SH3-like fold in diverse putative proteins tetramerizes into an oxidoreductase providing an antimicrobial resistance phenotype.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  7. Article
  8. Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020
    Review
  9. Article
  10. Article
  11. Mycobacterium tuberculosis Rv3651 is a triple sensor-domain protein.Protein science : a publication of the Protein Society · 2018
    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

11 authors at 2 institutions in 2 countries.

Mary OrtmayerManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Pierre LafiteManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Binuraj R K MenonManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Tewes TralauManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Karl FisherManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Lukas DenkhausManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Nigel S ScruttonManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Stephen E J RigbyManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Andrew W MunroManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Sam HayManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
David LeysManchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Czech Academy of Sciences, Institute of Biotechnology · CZInstitut de Chimie Organique et Analytique · FR

Funding

Biotechnology and Biological Sciences Research Council BB/E013007/1Biotechnology and Biological Sciences Research Council BB/E017010/1
6 · The paper itself

Abstract

The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases. The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine. The structure of the α subunit reveals that it is a haem-binding PAS domain, similar in structure to PAS gas sensors. The dimethylamine substrate forms part of a highly polarized oxygen-binding site, and directly assists oxygen activation by acting as both an electron and proton donor. Our data reveal that the ubiquitous PAS domain can make the transition from sensor to enzyme, suggesting that the PAS scaffold can support the development of artificial enzymes.

Indexed as

Binding SitesCoenzymesCrystallography, X-RayDimethylaminesFlavin MononucleotideHemeIron-Sulfur ProteinsModels, MolecularNADPOxidation-ReductionOxidoreductases, N-DemethylatingOxygenProtein DomainsProtein SubunitsPseudomonas mendocinaTetrahydrofolates5,6,7,8-tetrahydrofolic acidCoenzymesdimethylamineDimethylaminesFlavin MononucleotideHemeIron-Sulfur ProteinsNADPOxidoreductases, N-DemethylatingOxygenProtein SubunitsTetrahydrofolates

Identifiers

PMID27851736
OpenAlexW2554288123

What OpenQuestion holds

Textmetadata
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.