7oc0

Structure of Pseudomonas aeruginosa FabF mutant C164Q in complex with a ligand (2S,4R)-2-(thiophen-2-yl)thiazolidine-4-carboxylic acid

spinqualitylabelsall models 7oc0, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.78Å Ligands: DMS, MG, V7W Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed FabF (3-oxoacyl-[acyl-carrier-protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio-layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure-based design of FabF inhibitors was demonstrated through the validation of hits obtained from virtual screening. Screening a library of almost 5 million compounds resulted in 6 compounds for which binding into the malonyl-binding site of FabF was shown. For one of the hits, the crystal structure in complex with PaFabF was determined. Based on the obtained binding mode, analogues were designed and synthesised, but affinity could not be improved. This work has laid the foundation for structure-based exploration of PaFabF. An Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics.,Espeland LO, Georgiou C, Klein R, Bhukya H, Haug BE, Underhaug J, Mainkar PS, Brenk R ChemMedChem. 2021 Jun 29. doi: 10.1002/cmdc.202100302. PMID:34189850 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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