A mechanism of drug action revealed by structural studies of enoyl reductase.

Article Details

Citation

Baldock C, Rafferty JB, Sedelnikova SE, Baker PJ, Stuitje AR, Slabas AR, Hawkes TR, Rice DW

A mechanism of drug action revealed by structural studies of enoyl reductase.

Science. 1996 Dec 20;274(5295):2107-10.

PubMed ID
8953047 [ View in 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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Enoyl-[acyl-carrier-protein] reductase [NADH] FabIP0AEK4Details