The crystal structure of the Escherichia coli
enoyl reductase-NAD+-triclosan complex has been
determined at 2.5 Å resolution. The Ile192–Ser198
loop is either disordered or in an open conformation in
the previously reported structures of the enzyme. This
loop adopts a closed conformation in our structure, forming
van der Waals interactions with the inhibitor and hydrogen
bonds with the bound NAD+ cofactor. The opening
and closing of this flipping loop is likely an important
factor in substrate or ligand recognition. The closed conformation
of the loop appears to be a critical feature for the enhanced
binding potency of triclosan, and a key component in future
structure-based inhibitor design.