title: Structural characterisation of the fatty acid biosynthesis enzyme FabF from the pathogen Listeria monocytogenes.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, 2678, Australia.|Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia.
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Soares da Costa
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, 2678, Australia.|School of Chemistry and Molecular Biosciences and Institute for Molecular Bioscience (Division of Chemistry and Structural Biology) and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, 4072, Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Nanson
authors.affiliation: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, 2678, Australia.
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; C078182:beta-ketoacyl-acyl carrier protein synthase I; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase