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PDBsum entry 1uae

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Transferase PDB id
1uae
Jmol
Contents
Protein chain
418 a.a.
Ligands
UD1
FFQ
Waters ×422

References listed in PDB file
Key reference
Title 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.
Authors T.Skarzynski, A.Mistry, A.Wonacott, S.E.Hutchinson, V.A.Kelly, K.Duncan.
Ref. Structure, 1996, 4, 1465-1474. [DOI no: 10.1016/S0969-2126(96)00153-0]
PubMed id 8994972
Abstract
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.
Figure 3.
Figure 3. A stereo representation of the active site of MurA with a cross-section through the molecular surface of the enzyme (white dots) showing surface complementarity between the ligands and the protein (stick representation). UDP-GlcNAc and fosfomycin are represented as van der Waals spheres. Atoms are depicted in standard colours. Only residues mentioned in the text are shown, along with water molecules (represented as red crosses) trapped in the catalytic pocket. Figure was produced with the program QUANTA (Molecular Simulations Inc.).
The above figure is reprinted by permission from Cell Press: Structure (1996, 4, 1465-1474) copyright 1996.
Secondary reference #1
Title Cloning and sequencing of escherichia coli murz and purification of its product, A udp-N-Acetylglucosamine enolpyruvyl transferase.
Authors J.L.Marquardt, D.A.Siegele, R.Kolter, C.T.Walsh.
Ref. J Bacteriol, 1992, 174, 5748-5752.
PubMed id 1512209
Abstract
PROCHECK
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