ArticleThe Journal of antimicrobial chemotherapy2011
Mechanism and inhibition of the FabI enoyl-ACP reductase from Burkholderia pseudomallei.
Article in The Journal of antimicrobial chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Structural and Biochemical Studies on Klebsiella Pneumoniae Enoyl-ACP Reductase (FabI) Suggest Flexible Substrate Binding Site.The protein journal · 2024Article
- Glycosylated Flavonoid Compounds as Potent CYP121 Inhibitors ofBiomolecules · 2022Article
- Bacterial Enoyl-Reductases: The Ever-Growing List of Fabs, Their Mechanisms and Inhibition.Frontiers in microbiology · 2022Review
- Drug Discovery forInternational journal of molecular sciences · 2021Review
- Rationalizing the Binding Kinetics for the Inhibition of the Burkholderia pseudomallei FabI1 Enoyl-ACP Reductase.Biochemistry · 2017Article
- Article
- Selectivity of Pyridone- and Diphenyl Ether-Based Inhibitors for the Yersinia pestis FabV Enoyl-ACP Reductase.Biochemistry · 2016Article
- Escherichia coli ASKA Clone Library Harboring tRNA-Specific Adenosine Deaminase (tadA) Reveals Resistance towards Xanthorrhizol.Molecules (Basel, Switzerland) · 2015Article
- AFN-1252 is a potent inhibitor of enoyl-ACP reductase from Burkholderia pseudomallei--Crystal structure, mode of action, and biological activity.Protein science : a publication of the Protein Society · 2015Article
- A [(32)P]NAD(+)-based method to identify and quantitate long residence time enoyl-acyl carrier protein reductase inhibitors.Analytical biochemistry · 2015Article
- Efflux pump-mediated drug resistance in Burkholderia.Frontiers in microbiology · 2015Article
- Rational design of broad spectrum antibacterial activity based on a clinically relevant enoyl-acyl carrier protein (ACP) reductase inhibitor.The Journal of biological chemistry · 2014Article
- The Burkholderia pseudomallei enoyl-acyl carrier protein reductase FabI1 is essential for in vivo growth and is the target of a novel chemotherapeutic with efficacy.Antimicrobial agents and chemotherapy · 2014Article
- Substituted diphenyl ethers as a novel chemotherapeutic platform against Burkholderia pseudomallei.Antimicrobial agents and chemotherapy · 2014Article
- The Francisella tularensis FabI enoyl-acyl carrier protein reductase gene is essential to bacterial viability and is expressed during infection.Journal of bacteriology · 2013Article
- Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesAs an initial step in developing novel antibacterials against Burkholderia pseudomallei, we have characterized the FabI enoyl-ACP reductase homologues in the type II fatty acid biosynthesis pathway from this organism and performed an initial enzyme inhibition study.
methodsA BLAST analysis identified two FabI enoyl-ACP reductase homologues, bpmFabI-1 and bpmFabI-2, in the B. pseudomallei genome, which were cloned, overexpressed in Escherichia coli and purified. Steady-state kinetics was used to determine the reaction mechanism and the sensitivity of bpmFabI-1 to four diphenyl ether FabI inhibitors. The antibacterial activity of the inhibitors was assessed using a wild-type strain of Burkholderia thailandensis (E264) and an efflux pump mutant (Bt38).
resultsConsistent with its annotation as an enoyl-ACP reductase, bpmFabI-1 catalysed the NADH-dependent reduction of 2-trans-dodecenoyl-CoA via a sequential Bi Bi mechanism. In contrast, bpmFabI-2 was inactive with all substrates tested and only bpmfabI-1 was transcriptionally active under the growth conditions employed. The sensitivity of bpmFabI-1 to four diphenyl ethers was evaluated and in each case the compounds were slow-onset inhibitors with K(i) values of 0.5-2 nM. In addition, triclosan and PT01 had MIC values of 30 and 70 mg/L for B. pseudomallei as well as a wild-type strain of B. thailandensis (E264), but MIC values of <1 mg/L for the efflux pump mutant Bt38. A reduction in MIC values was also observed for the pump mutant strain with the other diphenyl ethers.
conclusionsProvided that efflux can be circumvented, bpmFabI-1 is a suitable target for drug discovery.
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