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

X Qiu; C A Janson; R I Court; M G Smyth; D J Payne; S S Abdel-Meguid

doi:10.1110/ps.8.11.2529

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PubMed · 10595560

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

X Qiu·C A Janson·R I Court·M G Smyth·D J Payne·S S Abdel-Meguid

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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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Amino Acid Sequence Anti-Infective Agents, Local Binding Sites Crystallography, X-Ray Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)Escherichia coli Hydrogen Bonding Isoleucine Models, Molecular Molecular Sequence Data NAD Oxidoreductases Protein Conformation Serine Triclosan Journal Article

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X Qiu, C A Janson, R I Court, M G Smyth, D J Payne, S S Abdel-Meguid. 1999. Molecular basis for triclosan activity involves a flipping loop in the active site.. https://doi.org/10.1110/ps.8.11.2529

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