Evidence map›Paper›PMID 25291014›Full record

ArticleJournal of the American Chemical Society2014

Detection of lipid-linked peptidoglycan precursors by exploiting an unexpected transpeptidase reaction.

Yuan Qiao, Matthew D Lebar, Kathrin Schirner, Kaitlin Schaefer, Hirokazu Tsukamoto, Daniel Kahne, Suzanne Walker

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

69 citing papers in PubMed, 112 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Lipid II unlocked: strategies for obtaining a major antibiotic target.Chemical communications (Cambridge, England) · 2025
    Review
  5. Article
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9 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Yuan QiaoChemical Biology Program, Harvard University , Cambridge, Massachusetts 02138, United States.
Matthew D Lebar
Kathrin Schirner
Kaitlin Schaefer
Hirokazu Tsukamoto
Daniel Kahne
Suzanne Walker
Harvard University · US

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
Targeting bacterial cell wall biogenesis for the development of novel antimicrobU19AI109764 · NIAID · HARVARD MEDICAL SCHOOL · PI KAHNE, DANIEL · 2014 to 2018
$25.2M
Studies Toward Hybrid Glycopeptide AntibioticsR01GM066174 · NIGMS · PRINCETON UNIVERSITY · PI KAHNE, DANIEL · 2002 to 2018
$8.9M
Mechanism and Inhibition of Enzymes that Assemble Bacterial Cell WallR01GM076710 · NIGMS · HARVARD MEDICAL SCHOOL · PI WALKER, SUZANNE · 2007 to 2019
$5.9M
Mechanistic studies on peptidoglycan tailoring that mediate biofilm stabilityF32GM103056 · NIGMS · HARVARD UNIVERSITY · PI LEBAR, MATTHEW DENNIS · 2012 to 2013
$101k
NIAID NIH HHS P01 AI083214NIAID NIH HHS U19 AI109764NIGMS NIH HHS F32 GM103056NIGMS NIH HHS F32GM103056NIGMS NIH HHS R01 GM066174NIGMS NIH HHS R01 GM076710
6 · The paper itself

Abstract

Penicillin-binding proteins (PBPs) are involved in the synthesis and remodeling of bacterial peptidoglycan (PG). Staphylococcus aureus expresses four PBPs. Genetic studies in S. aureus have implicated PBP4 in the formation of highly cross-linked PG, but biochemical studies have not reached a consensus on its primary enzymatic activity. Using synthetic Lipid II, we show here that PBP4 preferentially acts as a transpeptidase (TP) in vitro. Moreover, it is the PBP primarily responsible for incorporating exogenous d-amino acids into cellular PG, implying that it also has TP activity in vivo. Notably, PBP4 efficiently exchanges d-amino acids not only into PG polymers but also into the PG monomers Lipid I and Lipid II. This is the first demonstration that any TP domain of a PBP can activate the PG monomer building blocks. Exploiting the promiscuous TP activity of PBP4, we developed a simple, highly sensitive assay to detect cellular pools of lipid-linked PG precursors, which are of notoriously low abundance. This method, which addresses a longstanding problem, is useful for assessing how genetic and pharmacological perturbations affect precursor levels, and may facilitate studies to elucidate antibiotic mechanism of action.

Indexed as

Staphylococcus aureusBacterial ProteinsMonosaccharidesOligopeptidesPenicillin-Binding ProteinsPeptidoglycanPeptidyl TransferasesProtein Structure, TertiaryUridine Diphosphate N-Acetylmuramic AcidBacterial Proteinslipid IMonosaccharidesmuramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenolOligopeptidesPenicillin-Binding ProteinsPeptidoglycanPeptidyl TransferasesUridine Diphosphate N-Acetylmuramic Acid

Identifiers

PMID25291014
PMCPMC4210121
OpenAlexW2167800069

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.