Evidence map›Paper›PMID 28553948›Full record

ArticleNature chemical biology2017

Lipid II overproduction allows direct assay of transpeptidase inhibition by β-lactams.

Yuan Qiao, Veerasak Srisuknimit, Frederick Rubino, Kaitlin Schaefer, Natividad Ruiz, Suzanne Walker, Daniel Kahne

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Lipid II unlocked: strategies for obtaining a major antibiotic target.Chemical communications (Cambridge, England) · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Revisiting the Role of VraTSR inJournal of bacteriology · 2022
    Article
  19. Article
  20. Metal cofactor stabilization by a partner protein is a widespread strategy employed for amidase activation.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yuan QiaoDepartment of Microbiology and Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Veerasak SrisuknimitDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Frederick RubinoDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.ORCID http://orcid.org/0000-0002-7149-6088
Kaitlin SchaeferDepartment of Microbiology and Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Natividad RuizDepartment of Microbiology, Ohio State University, Columbus, Ohio, USA.
Suzanne WalkerDepartment of Microbiology and Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Daniel KahneDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Harvard University · USThe Ohio State University · US

Funding

Targeting bacterial cell wall biogenesis for the development of novel antimicrobU19AI109764 · NIAID · HARVARD MEDICAL SCHOOL · PI BERNHARDT, THOMAS G · 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
Envelope Biogenesis in Gram-negative BacteriaR01GM100951 · NIGMS · OHIO STATE UNIVERSITY · PI RUIZ, NATIVIDAD · 2012 to 2023
$3.7M
NIAID NIH HHS U19 AI109764NIGMS NIH HHS R01 GM066174NIGMS NIH HHS R01 GM076710NIGMS NIH HHS R01 GM100951
6 · The paper itself

Abstract

Peptidoglycan is an essential crosslinked polymer that surrounds bacteria and protects them from osmotic lysis. β-lactam antibiotics target the final stages of peptidoglycan biosynthesis by inhibiting the transpeptidases that crosslink glycan strands to complete cell wall assembly. Characterization of transpeptidases and their inhibition by β-lactams have been hampered by lack of access to a suitable substrate. We describe a general approach to accumulate Lipid II in bacteria and to obtain large quantities of this cell wall precursor. We demonstrate the utility of this strategy by isolating Staphylococcus aureus Lipid II and reconstituting the synthesis of crosslinked peptidoglycan by the essential penicillin-binding protein 2 (PBP2), which catalyzes both glycan polymerization and transpeptidation. We also show that we can compare the potencies of different β-lactams by directly monitoring transpeptidase inhibition. The methods reported here will enable a better understanding of cell wall biosynthesis and facilitate studies of next-generation transpeptidase inhibitors.

Indexed as

Bacterial Proteinsbeta-LactamsCell WallLipidsMolecular StructurePenicillin-Binding ProteinsPeptidyl TransferasesStaphylococcus aureusBacterial Proteinsbeta-LactamsLipidsPenicillin-Binding ProteinsPeptidyl Transferases

Identifiers

PMID28553948
PMCPMC5478438
OpenAlexW2618803170

What OpenQuestion holds

Textmetadata
LicenceTDM
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.