An Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics.

ABSTRACT: 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

SUBMITTER: Espeland LO 

PROVIDER: S-EPMC8518799 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature