The crystal structures of the compounds 122 and 124 in complex with PaFabF 164A were determined (Figure and, Figure and). The heterocycle of both ligands is positioned as in the parent compound 21(Figure ) forming water-mediated contacts Ala280, Gly279, Asp266 and Asn404 as well as π -π stacking interactions with Phe398. Further, 122 forms additional water-mediated hydrogen bonds with the catalytic histidines. In contrast, the elongated carbon chain of 124 allowed the carboxylate group to be positioned to form salt bridges with the catalytic histidines. In addition, this location of the carboxylate group allowed for formation of a water bridge to the back-bone of Phe400. The direct interactions of 124 with the catalytic histidines probably contribute to the relatively strong binding of this compound.