1cwu
From Proteopedia
BRASSICA NAPUS ENOYL ACP REDUCTASE A138G MUTANT COMPLEXED WITH NAD+ AND THIENODIAZABORINE
Structural highlights
Function[FABI_BRANA] Catalyzes the NAD-dependent reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Catalyzes the last reduction step in the de novo synthesis cycle of fatty acids. Involved in the elongation cycle of fatty acids which are used in lipid metabolism. Required for normal plant growth (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEnoyl 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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