Evidence map›Paper›PMID 27226570›Full record

ArticleThe Journal of biological chemistry2016

New Insight into the Catalytic Mechanism of Bacterial MraY from Enzyme Kinetics and Docking Studies.

Yao Liu, João P G L M Rodrigues, Alexandre M J J Bonvin, Esther A Zaal, Celia R Berkers, Michal Heger, Katarzyna Gawarecka, Ewa Swiezewska, Eefjan Breukink, Maarten R Egmond

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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Molecular action of NZ2114, a superior plectasin derivative.npj antimicrobials and resistance · 2026
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  6. Proteome-wide bioinformatic annotation and functional validation of the monotopic phosphoglycosyl transferase superfamily.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  8. Review
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  10. Review
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  12. Review
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  15. Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. 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.

Yao LiuFrom Institute of Biomembranes, Department of Membrane Biochemistry and Biophysics, Utrecht University, 3584 CH, Utrecht, the Netherlands.
João P G L M Rodriguesthe Departments of Computational Structural Biology and.
Alexandre M J J Bonvinthe Departments of Computational Structural Biology and.
Esther A ZaalBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH, Utrecht, the Netherlands.
Celia R BerkersBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH, Utrecht, the Netherlands.
Michal Hegerthe Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands, and.
Katarzyna Gawareckathe Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Ewa Swiezewskathe Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Eefjan BreukinkFrom Institute of Biomembranes, Department of Membrane Biochemistry and Biophysics, Utrecht University, 3584 CH, Utrecht, the Netherlands, E.J.Breukink@uu.nl.
Maarten R EgmondFrom Institute of Biomembranes, Department of Membrane Biochemistry and Biophysics, Utrecht University, 3584 CH, Utrecht, the Netherlands.
Utrecht University · NLInstitute of Biochemistry and Biophysics, Polish Academy of Sciences · PLUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phospho-MurNAc-pentapeptide translocase (MraY) catalyzes the synthesis of Lipid I, a bacterial peptidoglycan precursor. As such, MraY is essential for bacterial survival and therefore is an ideal target for developing novel antibiotics. However, the understanding of its catalytic mechanism, despite the recently determined crystal structure, remains limited. In the present study, the kinetic properties of Bacillus subtilis MraY (BsMraY) were investigated by fluorescence enhancement using dansylated UDP-MurNAc-pentapeptide and heptaprenyl phosphate (C35-P, short-chain homolog of undecaprenyl phosphate, the endogenous substrate of MraY) as second substrate. Varying the concentrations of both of these substrates and fitting the kinetics data to two-substrate models showed that the concomitant binding of both UDP-MurNAc-pentapeptide-DNS and C35-P to the enzyme is required before the release of the two products, Lipid I and UMP. We built a model of BsMraY and performed docking studies with the substrate C35-P to further deepen our understanding of how MraY accommodates this lipid substrate. Based on these modeling studies, a novel catalytic role was put forward for a fully conserved histidine residue in MraY (His-289 in BsMraY), which has been experimentally confirmed to be essential for MraY activity. Using the current model of BsMraY, we propose that a small conformational change is necessary to relocate the His-289 residue, such that the translocase reaction can proceed via a nucleophilic attack of the phosphate moiety of C35-P on bound UDP-MurNAc-pentapeptide.

Indexed as

Amino Acid SubstitutionBacillus subtilisBacterial ProteinsCatalysisKineticsModels, MolecularMonosaccharidesMutagenesis, Site-DirectedOligopeptidesPolyisoprenyl PhosphatesProtein ConformationRecombinant ProteinsSubstrate SpecificityTransferasesTransferases (Other Substituted Phosphate Groups)Uridine Diphosphate N-Acetylmuramic AcidBacterial Proteinslipid IMonosaccharidesmraY protein, BacteriaOligopeptidesPolyisoprenyl PhosphatesRecombinant ProteinsTransferasesTransferases (Other Substituted Phosphate Groups)UDP-N-acetylmuramic acid pentapeptideUridine Diphosphate N-Acetylmuramic AcidUridine MonophosphatedockingenzymeHADDOCKheliceskineticsmechanismMraYphosphatestructural modelstructure-function

Identifiers

PMID27226570
PMCPMC4946923
OpenAlexW2406050178

What OpenQuestion holds

Textmetadata
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Registered trials

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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.