Crystal structures of pseudomonas aeruginosa Enoyl-ACP reductase (FabI) in the presence and absence of NAD+ and triclosan

Enoyl-acyl carrier protein (ACP) reductases (ENRs) are enzymes involved in the final reduction in the bacterial fatty acid biosynthesis (FAS II) pathway. Based on their amino-acid sequences, ENRs have been classified as FabI, FabK, FabL, and FabV. Among them, FabI is highly conserved among most bacteria and many ligands have been designed and tested for their inhibitory activities against FabI. In this study, we report crystal structures of FabI from Pseudomonas aeruginosa (PaFabI) in its apo and ternary complex with NAD⁺ and triclosan at 2.6 and 1.8 Å resolutions, respectively. Structural comparison with apo and ternary complex indicates that triclosan leads to ordering of the substrate-binding loop like other previously reported FabI structures. Depending on the conformations of the substrate-binding loop, there are variations in the binding affinity of FabI and triclosan. PaFabI displays a relatively higher affinity toward triclosan in comparison with other FabIs, and this corresponds to its conformation of the substrate-binding loop.