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Molecular basis for triclosan activity involves a flipping loop in the active site
Author(s) -
Qiu Xiayang,
AbdelMeguid Sherin S.,
Janson Cheryl A.,
Court Robert I.,
Smyth Martin G.,
Payne David J.
Publication year - 1999
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.8.11.2529
Subject(s) - nad+ kinase , triclosan , stereochemistry , cofactor , chemistry , hydrogen bond , active site , oxidoreductase , loop (graph theory) , ligand (biochemistry) , conformational change , hydrolase , van der waals force , protein structure , binding site , reductase , substrate (aquarium) , crystallography , enzyme , biochemistry , biology , molecule , receptor , medicine , ecology , mathematics , organic chemistry , pathology , combinatorics
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.