ArticleProceedings of the National Academy of Sciences of the United States of America2007
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 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
48 citing papers in PubMed.
- Bioactivity-driven prediction of antibacterial synergy using machine learning models.PLoS computational biology · 2026Article
- Synthesis, Biological Evaluation, and Molecular Docking Studies of 2r,3t,4c-Configured C-Furanosidic LpxC Inhibitors.Archiv der Pharmazie · 2026Article
- ComparativeVeterinary world · 2026Article
- Biology of novel LpxC inhibitors forMicrobiology spectrum · 2026Article
- Metabolism-dependent succinylation governs resource allocation for antibiotic resistance.Science advances · 2025Article
- Review on Current Research on Biosynthesis of Biosurfactants and the Regulation Influenced by Metal Ions.Journal of microbiology and biotechnology · 2025Review
- Development of Fragment-Based Inhibitors of the Bacterial Deacetylase LpxC with Low Nanomolar Activity.Journal of medicinal chemistry · 2024Article
- Novel Hydroxamic Acids Containing Aryl-Substituted 1,2,4- or 1,3,4-Oxadiazole Backbones and an Investigation of Their Antibiotic Potentiation Activity.International journal of molecular sciences · 2023Article
- Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens.Science translational medicine · 2023Article
- Comparative Assessment of Docking Programs for Docking and Virtual Screening of Ribosomal Oxazolidinone Antibacterial Agents.Antibiotics (Basel, Switzerland) · 2023Article
- Microbial Genomics: Innovative Targets and Mechanisms.Antibiotics (Basel, Switzerland) · 2023Review
- Uncovering lipopolysaccharide regulation in bacteria via the critical lipid binding tunnel of YciS/YciM.iScience · 2022Article
- Structure-Kinetic Relationship Studies for the Development of Long Residence Time LpxC Inhibitors.Journal of medicinal chemistry · 2022Article
- Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia.FEMS microbes · 2022Article
- Antibiotic Therapy of Plague: A Review.Biomolecules · 2021Review
- Structure- and Ligand-Dynamics-Based Design of Novel Antibiotics Targeting Lipid A Enzymes LpxC and LpxH in Gram-Negative Bacteria.Accounts of chemical research · 2021Review
- The Complex Structure of Protein AaLpxC fromMolecules (Basel, Switzerland) · 2021Article
- Correlating Drug-Target Residence Time and Post-antibiotic Effect: Insight into Target Vulnerability.ACS infectious diseases · 2020Article
- Application of LpxC enzyme inhibitor to inhibit some fast-growing bacteria in human gut bacterial culturomics.BMC microbiology · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
Abstract
The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC-CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage.
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.