ReviewCurrent pharmaceutical biotechnology2008
Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis.
Review in Current pharmaceutical biotechnology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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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.
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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
71 citing papers in PubMed, 153 citations in OpenAlex.
- Control Targets in Plant-Pathogenic Bacteria: From Growth-Essential Processes to Anti-Virulence Strategies and Candidate Targets inPlants (Basel, Switzerland) · 2026Review
- Control of the committed step in lipopolysaccharide biosynthesis.The Journal of biological chemistry · 2026Review
- Biology of novel LpxC inhibitors forMicrobiology spectrum · 2026Article
- Targeting Bacterial Cell Wall Synthesis: Structural Insights and Emerging Therapeutic Strategies.Pharmaceutics · 2026Review
- Recent advances in small molecule LpxC inhibitors against gram-negative bacteria (2014-2024).Frontiers in microbiology · 2025Review
- Article
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Development of Fragment-Based Inhibitors of the Bacterial Deacetylase LpxC with Low Nanomolar Activity.Journal of medicinal chemistry · 2024Article
- Computational prediction of crucial genes involved in gonorrhea infection and neoplastic cell transformation: A multiomics approach.Microbial pathogenesis · 2024Article
- Advances in Development of Novel Therapeutic Strategies against Multi-Drug ResistantAntibiotics (Basel, Switzerland) · 2024Review
- Indole-based LpxC (UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosaminedeacetylase) inhibitors for3 Biotech · 2023Article
- Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives.Molecules (Basel, Switzerland) · 2023Review
- 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
- Acclimation to Nutritional Immunity and Metal Intoxication Requires Zinc, Manganese, and Copper Homeostasis in the PathogenicFrontiers in cellular and infection microbiology · 2022Review
- Checkpoints That Regulate Balanced Biosynthesis of Lipopolysaccharide and Its Essentiality inInternational journal of molecular sciences · 2021Review
- The Complex Structure of Protein AaLpxC fromMolecules (Basel, Switzerland) · 2021Article
- Regulation of the First Committed Step in Lipopolysaccharide Biosynthesis Catalyzed by LpxC Requires the Essential Protein LapC (YejM) and HslVU Protease.International journal of molecular sciences · 2020Article
- The essential inner membrane protein YejM is a metalloenzyme.Scientific reports · 2020Article
11 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Multi-drug resistant (MDR), pathogenic Gram-negative bacteria pose a serious health threat, and novel antibiotic targets must be identified to combat MDR infections. One promising target is the zinc-dependent metalloamidase UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), which catalyzes the committed step of lipid A (endotoxin) biosynthesis. LpxC is an essential, single copy gene that is conserved in virtually all Gram-negative bacteria. LpxC structures, revealed by NMR and X-ray crystallography, demonstrate that LpxC adopts a novel 'beta-alpha-alpha-beta sandwich' fold and encapsulates the acyl chain of the substrate with a unique hydrophobic passage. Kinetic analysis revealed that LpxC functions by a general acid-base mechanism, with a glutamate serving as the general base. Many potent LpxC inhibitors have been identified, and most contain a hydroxamate group targeting the catalytic zinc ion. Although early LpxC-inhibitors were either narrow-spectrum antibiotics or broad-spectrum in vitro LpxC inhibitors with limited antibiotic properties, the recently discovered compound CHIR-090 is a powerful antibiotic that controls the growth of Escherichia coli and Pseudomonas aeruginosa, with an efficacy rivaling that of the FDA-approved antibiotic ciprofloxacin. CHIR-090 inhibits a wide range of LpxC enzymes with sub-nanomolar affinity in vitro, and is a two-step, slow, tight-binding inhibitor of Aquifex aeolicus and E. coli LpxC. The success of CHIR-090 suggests that potent LpxC-targeting antibiotics may be developed to control a broad range of Gram-negative bacteria.
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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.