Download MendeleyMolecular basis for triclosan activity involves a flipping loop in the active site.
Qiu, X., Janson, C.A., Court, R.I., Smyth, M.G., Payne, D.J., Abdel-Meguid, S.S.(1999) Protein Sci 8: 2529-2532
- PubMed: 10595560
- DOI: https://doi.org/10.1110/ps.8.11.2529
- Primary Citation of Related Structures:
1C14 - PubMed Abstract:
The crystal structure of the Escherichia coli enoyl reductase-NAD+-triclosan complex has been determined at 2.5 A 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.
Organizational Affiliation:
Department of Structural Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. [email protected]
