Abstract
MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas aeruginosa performing one of the key membrane steps of peptidoglycan synthesis catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP-GlcNAc and compared it with the previously solved complex from E. coli. The structure reveals a large-scale conformational change in the relative orientations of the N- and C-terminal domains, which has the effect of widening the cofactor binding site and displacing the UDP-GlcNAc donor. These results suggest new opportunities to design potent inhibitors of peptidoglycan biosynthesis.
MeSH terms
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Amino Acid Sequence
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Bacterial Outer Membrane Proteins / chemistry*
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Bacterial Outer Membrane Proteins / metabolism
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Crystallization
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Crystallography, X-Ray
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Fluorometry
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Models, Molecular
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Molecular Sequence Data
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N-Acetylglucosaminyltransferases / chemistry*
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N-Acetylglucosaminyltransferases / metabolism
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Peptidoglycan / chemistry
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Peptidoglycan / metabolism
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Pseudomonas aeruginosa / enzymology
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Uridine Diphosphate N-Acetylglucosamine / chemistry*
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Uridine Diphosphate N-Acetylglucosamine / metabolism
Substances
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Bacterial Outer Membrane Proteins
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Peptidoglycan
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Recombinant Proteins
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Uridine Diphosphate N-Acetylglucosamine
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N-Acetylglucosaminyltransferases
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UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase