Molecular basis for triclosan activity involves a flipping loop in the active site

Abstract

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.