Evidence map›Paper›PMID 27590338›Full record

ArticleThe Journal of biological chemistry2016

Ser/Thr Phosphorylation Regulates the Fatty Acyl-AMP Ligase Activity of FadD32, an Essential Enzyme in Mycolic Acid Biosynthesis.

Nguyen-Hung Le, Virginie Molle, Nathalie Eynard, Mathieu Miras, Alexandre Stella, Fabienne Bardou, Ségolène Galandrin, Valérie Guillet, Gwenaëlle André-Leroux, Marco Bellinzoni and 5 more

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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 21% 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, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Comparative transcriptomic signatures of virulent and attenuatedFrontiers in cellular and infection microbiology · 2025
    Article
  4. Article
  5. Frontiers in microbiology · 2021
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. 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

15 authors at 3 institutions in 1 country.

Nguyen-Hung LeFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Virginie Mollethe Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier, CNRS UMR 5235, Place Eugène Bataillon, 34095 Montpellier Cedex 05, and.
Nathalie EynardFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Mathieu MirasFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Alexandre StellaFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Fabienne BardouFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Ségolène GalandrinFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Valérie GuilletFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Gwenaëlle André-Lerouxthe Institut Pasteur, Unité de Microbiologie Structurale, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
Marco Bellinzonithe Institut Pasteur, Unité de Microbiologie Structurale, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
Pedro Alzarithe Institut Pasteur, Unité de Microbiologie Structurale, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
Lionel MoureyFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Odile Burlet-SchiltzFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS.
Mamadou DafféFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, mamadou.daffe@ipbs.fr.
Hedia MarrakchiFrom the Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, hedia.marrakchi@ipbs.fr.
Institut de Pharmacologie et de Biologie Structurale · FRInstitut Pasteur · FRCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mycolic acids are essential components of the mycobacterial cell envelope, and their biosynthetic pathway is a well known source of antituberculous drug targets. Among the promising new targets in the pathway, FadD32 is an essential enzyme required for the activation of the long meromycolic chain of mycolic acids and is essential for mycobacterial growth. Following the in-depth biochemical, biophysical, and structural characterization of FadD32, we investigated its putative regulation via post-translational modifications. Comparison of the fatty acyl-AMP ligase activity between phosphorylated and dephosphorylated FadD32 isoforms showed that the native protein is phosphorylated by serine/threonine protein kinases and that this phosphorylation induced a significant loss of activity. Mass spectrometry analysis of the native protein confirmed the post-translational modifications and identified Thr-552 as the phosphosite. Phosphoablative and phosphomimetic FadD32 mutant proteins confirmed both the position and the importance of the modification and its correlation with the negative regulation of FadD32 activity. Investigation of the mycolic acid condensation reaction catalyzed by Pks13, involving FadD32 as a partner, showed that FadD32 phosphorylation also impacts the condensation activity. Altogether, our results bring to light FadD32 phosphorylation by serine/threonine protein kinases and its correlation with the enzyme-negative regulation, thus shedding a new horizon on the mycolic acid biosynthesis modulation and possible inhibition strategies for this promising drug target.

Indexed as

Amino Acid SubstitutionBacterial ProteinsLigasesMutation, MissenseMycobacterium tuberculosisMycolic AcidsPhosphorylationPolyketide SynthasesBacterial ProteinsLigasesMycolic Acidspolyketide synthase Pks13, Mycobacterium tuberculosisPolyketide Synthasescell walllipid metabolismmycobacteriapost-translational modification (PTM)protein phosphorylation

Identifiers

PMID27590338
PMCPMC5077212
OpenAlexW2509989231

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.