1QSG

CRYSTAL STRUCTURE OF ENOYL REDUCTASE INHIBITION BY TRICLOSAN

Summary for 1QSG

• Entry DOI: 10.2210/pdb1qsg/pdb
• Related: 1DFG 1DFH 1DFI
• Descriptor: ENOYL-[ACYL-CARRIER-PROTEIN] REDUCTASE, alpha-D-glucopyranose, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: enoyl reductase, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 8
• Total formula weight: 234466.59

Authors

Stewart, M.J.,Parikh, S.,Xiao, G.,Tonge, P.J.,Kisker, C. (deposition date: 1999-06-21, release date: 1999-07-21, Last modification date: 2023-08-16)

Primary citation

Stewart, M.J.,Parikh, S.,Xiao, G.,Tonge, P.J.,Kisker, C.
Structural basis and mechanism of enoyl reductase inhibition by triclosan.
J.Mol.Biol., 290:859-865, 1999

PubMed Abstract: The enoyl-acyl carrier protein reductase (ENR) is involved in bacterial fatty acid biosynthesis and is the target of the antibacterial diazaborine compounds and the front-line antituberculosis drug isoniazid. Recent studies suggest that ENR is also the target for the broad-spectrum biocide triclosan. The 1.75 A crystal structure of EnvM, the ENR from Escherichia coli, in complex with triclosan and NADH reveals that triclosan binds specifically to EnvM. These data provide a molecular mechanism for the antibacterial activity of triclosan and substantiate the hypothesis that its activity results from inhibition of a specific cellular target rather than non-specific disruption of the bacterial cell membrane. This has important implications for the emergence of drug-resistant bacteria, since triclosan is an additive in many personal care products such as toothpastes, mouthwashes and soaps. Based on this structure, rational design of triclosan derivatives is possible which might be effective against recently identified triclosan-resistant bacterial strains.

PubMed: 10398587
DOI: 10.1006/jmbi.1999.2907

Experimental method

X-RAY DIFFRACTION (1.75 Å)