A study of the structure-activity relationship for diazaborine inhibition of Escherichia coli enoyl-ACP reductase.
J Mol Biol
; 309(1): 171-80, 2001 May 25.
Article
em En
| MEDLINE
| ID: mdl-11491286
ABSTRACT
Enoyl acyl carrier protein (ACP) reductase catalyses the last reductive step of fatty acid biosynthesis, reducing the enoyl group of a growing fatty acid chain attached to ACP to its acyl product using NAD(P)H as the cofactor. This enzyme is the target for the diazaborine class of antibacterial agents, the biocide triclosan, and one of the targets for the front-line anti-tuberculosis drug isoniazid. The structures of complexes of Escherichia coli enoyl-ACP reductase (ENR) from crystals grown in the presence of NAD+ and a family of diazaborine compounds have been determined. Analysis of the structures has revealed that a mobile loop in the structure of the binary complex with NAD+ becomes ordered on binding diazaborine/NAD+ but displays a different conformation in the two subunits of the asymmetric unit. The work presented here reveals how, for one of the ordered conformations adopted by the mobile loop, the mode of diazaborine binding correlates well with the activity profiles of the diazaborine family. Additionally, diazaborine binding provides insights into the pocket on the enzyme surface occupied by the growing fatty acid chain.
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Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
/
Compostos de Boro
/
Inibidores Enzimáticos
/
Escherichia coli
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Reino Unido