Evidence map›Paper›PMID 35199904›Full record

ArticleAngewandte Chemie (International ed. in English)2022

Tailored Pyridoxal Probes Unravel Novel Cofactor-Dependent Targets and Antibiotic Hits in Critical Bacterial Pathogens.

Martin Pfanzelt, Thomas E Maher, Ramona M Absmeier, Markus Schwarz, Stephan A Sieber

Open access · hybridAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Exploring antibiotic resistance with chemical tools.Chemical communications (Cambridge, England) · 2023
    Review
  11. Article
  12. Review
  13. Functionalised Cofactor Mimics for Interactome Discovery and Beyond.Angewandte Chemie (International ed. in English) · 2022
    Review
  14. 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

5 authors at 2 institutions in 2 countries.

Martin PfanzeltCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.ORCID 0000-0002-0870-7399
Thomas E MaherCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.ORCID 0000-0002-4395-3704
Ramona M AbsmeierCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.ORCID 0000-0002-9267-8358
Markus SchwarzCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.ORCID 0000-0002-3909-5532
Stephan A SieberCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.ORCID 0000-0002-9400-906X
Technical University of Munich · DELondon Biofoundry · GB

Funding

European Research Council 725085
6 · The paper itself

Abstract

Unprecedented bacterial targets are urgently needed to overcome the resistance crisis. Herein we systematically mine pyridoxal phosphate-dependent enzymes (PLP-DEs) in bacteria to focus on a target class which is involved in crucial metabolic processes. For this, we tailored eight pyridoxal (PL) probes bearing modifications at various positions. Overall, the probes exceeded the performance of a previous generation and provided a detailed map of PLP-DEs in clinically relevant pathogens including challenging Gram-negative strains. Putative PLP-DEs with unknown function were exemplarily characterized via in-depth enzymatic assays. Finally, we screened a panel of PLP binders for antibiotic activity and unravelled the targets of hit molecules. Here, an uncharacterized enzyme, essential for bacterial growth, was assigned as PLP-dependent cysteine desulfurase and confirmed to be inhibited by the marketed drug phenelzine. Our approach provides a basis for deciphering novel PLP-DEs as essential antibiotic targets along with corresponding ways to decipher small molecule inhibitors.

Indexed as

Anti-Bacterial AgentsPyridoxalBacteriaPyridoxal PhosphateAnti-Bacterial AgentsPyridoxalPyridoxal PhosphateAntibiotic Compound ScreeningCofactorsEnzyme CharacterisationProteomicsPyridoxal Phosphate-Dependent Enzymes

Identifiers

PMID35199904
PMCPMC9321722
OpenAlexW4213446466

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.