ArticleJournal of medicinal chemistry2013
Non-nucleoside inhibitors of BasE, an adenylating enzyme in the siderophore biosynthetic pathway of the opportunistic pathogen Acinetobacter baumannii.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Inhibition of Surfactin Biosynthesis in Bacillus Subtilis Using Cell-Permeable Adenylation Domain Inhibitors.Chembiochem : a European journal of chemical biology · 2025Article
- Molybdate uptake interplay with ROS tolerance modulates bacterial pathogenesis.Science advances · 2025Article
- Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains.Natural product reports · 2024Review
- Kinetic analysis of the three-substrate reaction mechanism of an NRPS-independent siderophore (NIS) synthetase.Methods in enzymology · 2024Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- In-Depth Analysis of the Role of the Acinetobactin Cluster in the Virulence ofFrontiers in microbiology · 2021Article
- Preacinetobactin not acinetobactin is essential for iron uptake by the BauA transporter of the pathogeneLife · 2018Article
- Crystal Structure of the Siderophore Binding Protein BauB Bound to an Unusual 2:1 Complex Between Acinetobactin and Ferric Iron.Biochemistry · 2018Article
- Structural Biology of Nonribosomal Peptide Synthetases.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Investigation and conformational analysis of fluorinated nucleoside antibiotics targeting siderophore biosynthesis.The Journal of organic chemistry · 2015Article
- General platform for systematic quantitative evaluation of small-molecule permeability in bacteria.ACS chemical biology · 2014Article
- Enterobactin-mediated delivery of β-lactam antibiotics enhances antibacterial activity against pathogenic Escherichia coli.Journal of the American Chemical Society · 2014Article
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9 authors.
Funding
Abstract
Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening against BasE, which is involved in siderophore biosynthesis in A. baumannii, and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a KD of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveals that they bind in a unique orientation in the active site, occupying all three substrate binding sites, and thus can be considered as multisubstrate inhibitors. These results provide a foundation for future studies aimed at increasing both enzyme potency and antibacterial activity.
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