1cwu
From Proteopedia
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BRASSICA NAPUS ENOYL ACP REDUCTASE A138G MUTANT COMPLEXED WITH NAD+ AND THIENODIAZABORINE
Overview
Enoyl acyl carrier protein reductase (ENR) is involved in fatty acid, biosynthesis. In Escherichia coli this enzyme is the target for the, experimental family of antibacterial agents, the diazaborines, and for, triclosan, a broad spectrum antimicrobial agent. Biochemical studies have, suggested that the mechanism of diazaborine inhibition is dependent on, NAD(+) and not NADH, and resistance of Brassica napus ENR to diazaborines, is thought to be due to the replacement of a glycine in the active site of, the E. coli enzyme by an alanine at position 138 in the plant homologue., We present here an x-ray analysis of crystals of B. napus ENR A138G grown, in the presence of either NAD(+) or NADH and the structures of the, corresponding ternary complexes with thienodiazaborine obtained either by, soaking the drug into the crystals or by co-crystallization of the mutant, with NAD(+) and diazaborine. Analysis of the ENR A138G complex with, diazaborine and NAD(+) shows that the site of diazaborine binding is, remarkably close to that reported for E. coli ENR. However, the structure, of the ternary ENR A138G-NAD(+)-diazaborine complex obtained using, co-crystallization reveals a previously unobserved conformational change, affecting 11 residues that flank the active site and move closer to the, nicotinamide moiety making extensive van der Waals contacts with, diazaborine. Considerations of the mode of substrate binding suggest that, this conformational change may reflect a structure of ENR that is, important in catalysis.
About this Structure
1CWU is a Single protein structure of sequence from Brassica napus with NAD and TDB as ligands. Active as [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Full crystallographic information is available from OCA.
Reference
Inhibitor binding studies on enoyl reductase reveal conformational changes related to substrate recognition., Roujeinikova A, Sedelnikova S, de Boer GJ, Stuitje AR, Slabas AR, Rafferty JB, Rice DW, J Biol Chem. 1999 Oct 22;274(43):30811-7. PMID:10521472[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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