4bnw

Crystal structure of 3-oxoacyl-(acyl-carrier-protein) reductase (FabG) from Pseudomonas aeruginosa in complex with an unknown ligand at 1. 6A resolution

spinqualitylabelsall models 4bnw, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bnw is a 4 chain structure with sequence from Pseae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PEG, PG4, PGE Related: 4bnt, 4bnu, 4bnv, 4bnx, 4bny, 4bnz, 4bo0, 4bo1, 4bo2, 4bo3, 4bo4, 4bo5, 4bo6, 4bo7, 4bo8, 4bo9 Activity: [acyl-carrier-protein_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number 1.1.1.100 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [FABG_PSEAE] Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis (By similarity). Publication Abstract from PubMed 3-oxo-acyl-acyl carrier protein (ACP) reductase (FabG) plays a key role in the bacterial fatty acid synthesis II system in pathogenic microorganisms, which has been recognized as a potential drug target. FabG catalyzes reduction of a 3-oxo-acyl-ACP intermediate during the elongation cycle of fatty acid biosynthesis. Here, we report gene deletion experiments that support the essentiality of this gene in P. aeruginosa and the identification of a number of small molecule FabG inhibitors with IC50 values in the nanomolar to low micromolar range and good physicochemical properties. Structural characterization of sixteen FabG-inhibitor complexes by X-ray crystallography revealed that the compounds bind at a novel allosteric site located at the FabG subunit-subunit interface. Inhibitor binding relies primarily on hydrophobic interactions, but specific hydrogen-bonds are also observed. Importantly, the binding cavity is formed upon complex formation and therefore would not be recognized by virtual screening approaches. The structure analysis further reveals that the inhibitors act by inducing conformational changes that propagate to the active site resulting in a displacement of the catalytic triad and the inability to bind NADPH. Discovery of an allosteric inhibitor binding site in 3-oxo-acyl-ACP reductase from Pseudomonas aeruginosa.,Cukier CD, Hope AG, Elamin AA, Moynie L, Schnell R, Schach S, Kneuper H, Singh M, Naismith JH, Lindqvist Y, Gray DW, Schneider G ACS Chem Biol. 2013 Sep 9. PMID:24015914 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-ketoacyl-ACP reductase

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