1DFG

X-RAY STRUCTURE OF ESCHERICHIA COLI ENOYL REDUCTASE WITH BOUND NAD AND BENZO-DIAZABORINE

Summary for 1DFG

• Entry DOI: 10.2210/pdb1dfg/pdb
• Descriptor: ENOYL ACYL CARRIER PROTEIN REDUCTASE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 2-(TOLUENE-4-SULFONYL)-2H-BENZO[D][1,2,3]DIAZABORININ-1-OL (3 entities in total)
• Functional Keywords: oxidoreductase, lipid biosynthesis, diazaborine
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 57450.59

Authors

Baldock, C.,Rafferty, J.B.,Rice, D.W. (deposition date: 1997-01-16, release date: 1998-01-28, Last modification date: 2024-04-03)

Primary citation

Baldock, C.,Rafferty, J.B.,Sedelnikova, S.E.,Baker, P.J.,Stuitje, A.R.,Slabas, A.R.,Hawkes, T.R.,Rice, D.W.
A mechanism of drug action revealed by structural studies of enoyl reductase.
Science, 274:2107-2110, 1996

PubMed Abstract: Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.

PubMed: 8953047
DOI: 10.1126/science.274.5295.2107

Experimental method

X-RAY DIFFRACTION (2.5 Å)