ArticleCell chemical biology2022
Identification of covalent inhibitors that disrupt M. tuberculosis growth by targeting multiple serine hydrolases involved in lipid metabolism.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- In silico identification of novel alpha/beta hydrolase fold domain-containing protein associated with virulence and antibiotic resistance in Nocardia farcinica (Strain: JJSBBCNF_01).Molecular diversity · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Covalent Inhibitors Targeting Mycobacterial Enzymes: Current Status, Challenges and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Advancements in Structural Basis of Covalent Inhibitors Targeting SARS-CoV-2 Essential Proteins.Current medicinal chemistry · 2025Review
- Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets.Cell chemical biology · 2024Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets.bioRxiv : the preprint server for biology · 2024Article
- Activity-based protein profiling of serine hydrolases and penicillin-binding proteins inFEMS microbes · 2024Article
- Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.Nature chemical biology · 2023Article
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Activity-based protein profiling in microbes and the gut microbiome.Current opinion in chemical biology · 2023Review
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- Chemical approaches to unraveling the biology of mycobacteria.Cell chemical biology · 2023Review
- Sequence and Structural Motifs Controlling the Broad Substrate Specificity of the Mycobacterial Hormone-Sensitive Lipase LipN.ACS omega · 2023Article
- Chemoproteomic Approaches for Unraveling Prokaryotic Biology.Israel journal of chemistry · 2023Article
- Strategies for Competitive Activity-Based Protein Profiling in Small Molecule Inhibitor Discovery and Characterization.Israel journal of chemistry · 2023Article
- Strategies for enriching and characterizing proteins with inhibitory properties on the yeast surface.Protein engineering, design & selection : PEDS · 2023Article
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screen a library of small molecules containing serine-reactive electrophiles and identify narrow-spectrum inhibitors of M. tuberculosis growth. Using these lead molecules, we perform competitive activity-based protein profiling and identify multiple SH targets, including enzymes with uncharacterized functions. Lipidomic analyses of compound-treated cultures reveal an accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis. Mutant analysis reveals a path to resistance via the synthesis of mycocerates, but not through mutations to SH targets. Our results suggest that simultaneous inhibition of multiple SH enzymes is likely to be an effective therapeutic strategy for the treatment of M. tuberculosis infections.
Indexed as
Identifiers
What OpenQuestion holds
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.