| Literature DB >> 8953047 |
C Baldock1, J B Rafferty, S E Sedelnikova, P J Baker, A R Stuitje, A R Slabas, T R Hawkes, D W Rice.
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.Entities:
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Year: 1996 PMID： 8953047 DOI： 10.1126/science.274.5295.2107
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728