Structural characterisation of the fatty acid biosynthesis enzyme FabF from the pathogen Listeria monocytogenes

Development of new antimicrobial agents is required against the causative agent for listeriosis, Listeria monocytogenes, as the number of drug resistant strains continues to increase. A promising target is the β-ketoacyl-acyl carrier protein synthase FabF, which participates in the catalysis of fatt...

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Bibliographic Details
Published in:Scientific reports 2017-01, Vol.7 (1), p.39277-39277, Article 39277
Main Authors: Soares da Costa, Tatiana P, Nanson, Jeffrey D, Forwood, Jade K
Format: Article
Language:English
Subjects:
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase - chemistry
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase - metabolism
Acyl carrier protein
Acyl carrier protein synthase
Antimicrobial agents
Catalysis
Catalytic Domain
Crystal structure
Crystallography, X-Ray
Drug development
Drug resistance
Elongation
Enzyme Inhibitors - metabolism
Fatty acids
Isoenzymes - chemistry
Isoenzymes - metabolism
Lipopolysaccharides
Lipoproteins
Listeria
Listeria monocytogenes
Listeria monocytogenes - genetics
Listeriosis
Models, Molecular
Phospholipids
Protein Binding
Protein Conformation
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Summary:Development of new antimicrobial agents is required against the causative agent for listeriosis, Listeria monocytogenes, as the number of drug resistant strains continues to increase. A promising target is the β-ketoacyl-acyl carrier protein synthase FabF, which participates in the catalysis of fatty acid synthesis and elongation, and is required for the production of phospholipid membranes, lipoproteins, and lipopolysaccharides. In this study, we report the 1.35 Å crystal structure of FabF from L. monocytogenes, providing an excellent platform for the rational design of novel inhibitors. By comparing the structure of L. monocytogenes FabF with other published bacterial FabF structures in complex with known inhibitors and substrates, we highlight conformational changes within the active site, which will need to be accounted for during drug design and virtual screening studies. This high-resolution structure of FabF represents an important step in the development of new classes of antimicrobial agents targeting FabF for the treatment of listeriosis.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep39277