Evidence map›Paper›PMID 31324846›Full record

ArticleScientific reports2019

Mutagenesis separates ATPase and thioesterase activities of the peroxisomal ABC transporter, Comatose.

David J Carrier, Carlo W T van Roermund, Theresia A Schaedler, Hong Lin Rong, Lodewijk IJlst, Ronald J A Wanders, Stephen A Baldwin, Hans R Waterham, Frederica L Theodoulou, Alison Baker

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

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  13. Peroxisomal Metabolite and Cofactor Transport in Humans.Frontiers in cell and developmental biology · 2020
    Review
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

10 authors at 3 institutions in 2 countries.

David J CarrierSchool of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Carlo W T van RoermundAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, Gastroenterology & Metabolism, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Theresia A SchaedlerPlant Sciences Department, Rothamsted Research, Harpenden, AL5 2JQ, UK.
Hong Lin RongSchool of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Lodewijk IJlstAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, Gastroenterology & Metabolism, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Ronald J A WandersAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, Gastroenterology & Metabolism, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Stephen A BaldwinSchool of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Hans R WaterhamAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, Gastroenterology & Metabolism, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Frederica L TheodoulouPlant Sciences Department, Rothamsted Research, Harpenden, AL5 2JQ, UK.ORCID http://orcid.org/0000-0002-8306-0716
Alison BakerSchool of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.baker@leeds.ac.uk.ORCID http://orcid.org/0000-0003-2181-4057
Amsterdam University Medical Centers · NLUniversity of Leeds · GBRothamsted Research · GB

Funding

RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/L001012/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/L001691/1
6 · The paper itself

Abstract

The peroxisomal ABC transporter, Comatose (CTS), a full length transporter from Arabidopsis has intrinsic acyl-CoA thioesterase (ACOT) activity, important for physiological function. We used molecular modelling, mutagenesis and biochemical analysis to identify amino acid residues important for ACOT activity. D863, Q864 and T867 lie within transmembrane helix 9. These residues are orientated such that they might plausibly contribute to a catalytic triad similar to type II Hotdog fold thioesterases. When expressed in Saccharomyces cerevisiae, mutation of these residues to alanine resulted in defective of β-oxidation. All CTS mutants were expressed and targeted to peroxisomes and retained substrate-stimulated ATPase activity. When expressed in insect cell membranes, Q864A and S810N had similar ATPase activity to wild type but greatly reduced ACOT activity, whereas the Walker A mutant K487A had greatly reduced ATPase and no ATP-dependent ACOT activity. In wild type CTS, ATPase but not ACOT was stimulated by non-cleavable C14 ether-CoA. ACOT activity was stimulated by ATP but not by non-hydrolysable AMPPNP. Thus, ACOT activity depends on functional ATPase activity but not vice versa, and these two activities can be separated by mutagenesis. Whether D863, Q864 and T867 have a catalytic role or play a more indirect role in NBD-TMD communication is discussed.

Indexed as

Adenosine TriphosphatasesAdenosine TriphosphateAnimalsArabidopsisArabidopsis ProteinsATP-Binding Cassette TransportersCatalytic DomainCell LineFatty Acid SynthasesHydrophobic and Hydrophilic InteractionsMembrane ProteinsModels, MolecularMutagenesis, Site-DirectedMutation, MissenseOleic AcidOxidation-ReductionAdenosine TriphosphatasesAdenosine TriphosphateArabidopsis ProteinsAt4g39850 protein, ArabidopsisATP-Binding Cassette TransportersFatty Acid SynthasesMembrane ProteinsOleic AcidRecombinant Proteinsthioesterase IIThiolester Hydrolases

Identifiers

PMID31324846
PMCPMC6642094
OpenAlexW2963929307

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.