ArticleThe Journal of biological chemistry2016
PqsBC, a Condensing Enzyme in the Biosynthesis of the Pseudomonas aeruginosa Quinolone Signal: CRYSTAL STRUCTURE, INHIBITION, AND REACTION MECHANISM.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
- Quorum sensing inhibition strategies for the control of Pseudomonas aeruginosa infections.World journal of microbiology & biotechnology · 2026Review
- A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection.Nature communications · 2025Article
- Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence.NPJ biofilms and microbiomes · 2024Article
- Relationship between Pyochelin andInternational journal of molecular sciences · 2024Review
- Biosynthetic flexibility of Pseudomonas aeruginosa leads to hydroxylated 2-alkylquinolones with proinflammatory host response.Communications chemistry · 2023Article
- Alkyl-quinolone-dependent quorum sensing controls prophage-mediated autolysis inFrontiers in cellular and infection microbiology · 2023Article
- Novel Antibiofilm Inhibitor Ginkgetin as an Antibacterial Synergist againstInternational journal of molecular sciences · 2022Article
- Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1 sub-unit.PLoS pathogens · 2021Article
- Biological and clinical significance of quorum sensing alkylquinolones: current analytical and bioanalytical methods for their quantification.Analytical and bioanalytical chemistry · 2021Review
- Signal Synthase-Type versus Catabolic Monooxygenases: Retracing 3-Hydroxylation of 2-Alkylquinolones and TheirApplied and environmental microbiology · 2021Article
- Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.European journal of medicinal chemistry · 2020Article
- Quantitative proteomic reveals gallium maltolate induces an iron-limited stress response and reduced quorum-sensing in Pseudomonas aeruginosa.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- α-proteobacteria synthesize biotin precursor pimeloyl-ACP using BioZ 3-ketoacyl-ACP synthase and lysine catabolism.Nature communications · 2020Article
- Photoinduced monooxygenation involving NAD(P)H-FAD sequential single-electron transfer.Nature communications · 2020Article
- Development and bioanalytical method validation of an LC-MS/MS assay for simultaneous quantitation of 2-alkyl-4(1H)-quinolones for application in bacterial cell culture and lung tissue.Analytical and bioanalytical chemistry · 2020Article
- How structural subtleties lead to molecular diversity for the type III polyketide synthases.The Journal of biological chemistry · 2019Review
- 3-Ketoacyl-ACP synthase (KAS) III homologues and their roles in natural product biosynthesis.MedChemComm · 2019Review
- Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition.Frontiers in cellular and infection microbiology · 2019Review
- Potential of theFrontiers in cellular and infection microbiology · 2019Article
- PqsL uses reduced flavin to produce 2-hydroxylaminobenzoylacetate, a preferred PqsBC substrate in alkyl quinolone biosynthesis inThe Journal of biological chemistry · 2018Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pseudomonas aeruginosaproduces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell-cell communication. In the alkylquinolone biosynthetic pathway, the β-ketoacyl-(acyl carrier protein) synthase III (FabH)-like enzyme PqsBC catalyzes the condensation of octanoyl-coenzyme A and 2-aminobenzoylacetate (2-ABA) to form the signal molecule 2-heptyl-4(1H)-quinolone. PqsBC, a potential drug target, is unique for its heterodimeric arrangement and an active site different from that of canonical FabH-like enzymes. Considering the sequence dissimilarity between the subunits, a key question was how the two subunits are organized with respect to the active site. In this study, the PqsBC structure was determined to a 2 Å resolution, revealing that PqsB and PqsC have a pseudo-2-fold symmetry that unexpectedly mimics the FabH homodimer. PqsC has an active site composed of Cys-129 and His-269, and the surrounding active site cleft is hydrophobic in character and approximately twice the volume of related FabH enzymes that may be a requirement to accommodate the aromatic substrate 2-ABA. From physiological and kinetic studies, we identified 2-aminoacetophenone as a pathway-inherent competitive inhibitor of PqsBC, whose fluorescence properties could be used forin vitrobinding studies. In a time-resolved setup, we demonstrated that the catalytic histidine is not involved in acyl-enzyme formation, but contributes to an acylation-dependent increase in affinity for the second substrate 2-ABA. Introduction of Asn into the PqsC active site led to significant activity toward the desamino substrate analog benzoylacetate, suggesting that the substrate 2-ABA itself supplies the asparagine-equivalent amino function that assists in catalysis.
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Registered trials
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