ArticleJournal of the American Chemical Society2014
Detection of lipid-linked peptidoglycan precursors by exploiting an unexpected transpeptidase reaction.
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.
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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.
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Who cites it
69 citing papers in PubMed, 112 citations in OpenAlex.
- Penicillin-Binding Protein-4 (PBP4) ofMicroorganisms · 2026Review
- SEDS glycosyltransferases inmSphere · 2025Article
- Dual Mechanisms of Action of a Halogenated Allyl Fatty Acid against Methicillin-ResistantACS omega · 2025Article
- Lipid II unlocked: strategies for obtaining a major antibiotic target.Chemical communications (Cambridge, England) · 2025Review
- Article
- Machine learning and cheminformatics-based Identification of lichen-derived compounds targeting mutant PBP4Molecular diversity · 2025Article
- The cell wall hydrolase MltG is essential to maintain cell wall homeostasis ofJournal of bacteriology · 2025Article
- Sequestration of dead-end undecaprenyl phosphate-linked oligosaccharide intermediate.Microbiology (Reading, England) · 2025Article
- Pbp4 provides transpeptidase activity to the FtsW-PbpB peptidoglycan synthase to drive cephalosporin resistance inAntimicrobial agents and chemotherapy · 2024Article
- Phage protein Gp11 blocksmBio · 2024Article
- Development of phenyl-urea-based small molecules that target penicillin-binding protein 4.Chemical biology & drug design · 2024Article
- Noninvasive Analysis of Peptidoglycan from Living Animals.Bioconjugate chemistry · 2024Article
- Cryo-EM structure of the bacterial divisome core complex and antibiotic target FtsWIQBL.Nature microbiology · 2023Article
- Growth rate is modulated by monitoring cell wall precursors in Bacillus subtilis.Nature microbiology · 2023Article
- N-Amidation of Nitrogen-Containing Heterocyclic Compounds: Can We Apply Enzymatic Tools?Bioengineering (Basel, Switzerland) · 2023Review
- Real-time non-invasive fluorescence imaging of gut commensal bacteria to detect dynamic changes in the microbiome of live mice.Cell chemical biology · 2022Article
- Imitate to illuminate: labeling of bacterial peptidoglycan with fluorescent and bio-orthogonal stem peptide-mimicking probes.RSC chemical biology · 2022Review
- Intrinsically disordered protein regions are required for cell wall homeostasis inGenes & development · 2022Article
- The Bacterial Cell Wall: From Lipid II Flipping to Polymerization.Chemical reviews · 2022Review
- Chemical Reporters for Bacterial Glycans: Development and Applications.Chemical reviews · 2022Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.