Molecular basis for triclosan activity involves a flipping loop in the active site |
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Authors: | Qiu X Janson C A Court R I Smyth M G Payne D J Abdel-Meguid S S |
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Institution: | Department of Structural Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xiayang_qiu-1@sbphrd.com |
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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. |
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Keywords: | antibiotics crystal structure enoyl reductase fatty acid biosynthesis NAD+ triclosan |
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