Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

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. © 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.


Ludvik Olai Espeland, Charis Georgiou, Raphael Klein, Hemalatha Bhukya, Bengt Erik Haug, Jarl Underhaug, Prathama S Mainkar, Ruth Brenk. An Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics. ChemMedChem. 2021 Sep 06;16(17):2715-2726

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 34189850

View Full Text