1uae

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spinqualitylabelsall models 1uae, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF UDP-N-ACETYLGLUCOSAMINE ENOLPYRUVYL TRANSFERASE

Overview

BACKGROUND: UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyses the first committed step of bacterial cell wall biosynthesis and, is a target for the antibiotic fosfomycin. The only other known, enolpyruvyl transferase is 5-enolpyruvylshikimate-3-phosphate (EPSP), synthase, an enzyme involved in the shikimic acid pathway and the target, for the herbicide glyphosate. Inhibitors of enolpyruvyl transferases are, of biotechnological interest as MurA and EPSP synthase are found, exclusively in plants and microbes. RESULTS: The crystal structure of, Escherichia coli MurA complexed with UDP-N-acetylglucosamine (UDP-GlcNAc), and fosfomycin has been determined at 1.8 A resolution. The structure, consists of two domains with the active site located between them. The, domains have a very similar secondary structure, and the overall protein, architecture is similar to that of EPSP synthase. The fosfomycin molecule, is covalently bound to the cysteine residue Cys115, whereas UDP-GlcNAc, makes several hydrogen-bonding interactions with residues from both, domains. CONCLUSIONS: The present structure reveals the mode of binding of, the natural substrate UDP-GlcNAc and of the drug fosfomycin, and provides, information on the residues involved in catalysis. These results should, aid the design of inhibitors which would interfere with enzyme-catalyzed, reactions in the early stage of the bacterial cell wall biosynthesis., Furthermore, the crystal structure of MurA provides a model for predicting, active-site residues in EPSP synthase that may be involved in catalysis, and substrate binding.

About this Structure

1UAE is a Single protein structure of sequence from Escherichia coli with UD1 and FCN as ligands. Active as UDP-N-acetylglucosamine 1-carboxyvinyltransferase, with EC number 2.5.1.7 Full crystallographic information is available from OCA.

Reference

Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin., Skarzynski T, Mistry A, Wonacott A, Hutchinson SE, Kelly VA, Duncan K, Structure. 1996 Dec 15;4(12):1465-74. PMID:8994972

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