Two hit compounds (27 and 33) bind in the fatty acid binding site, in the same location as the substrate fatty acid tail and the hydrophobic part of cerulenin bind (Figure and Figure ). These compounds were found in both pockets of the dimer. The binding site is formed mostly by hydrophobic amino acids and no hydrogen bonds between the ligands and the protein were found in the structures. Binding of these ligands is accompanied by a conformational change enlarging this pocket compared to the apo state (Figure and). The position of these fragments overlaps well with the hydrophobic tail of the covalent inhibitor cerulenin (Figure , Table ). The reactive warhead of cerulenin bound to Cys164 (PaFabF numbering) is placed just next to the fragments. It appears therefore feasible to optimize these fragments by linking them to warheads suitable to react with cysteine residues to obtain covalent inhibitors.