Characterization of a beta -N-acetylglucosaminidase of Escherichia coli and elucidation of its role in muropeptide recycling and beta -lactamase induction.
Using the known mapping position the gene encoding a beta-1, 4-N-acetylglucosaminidase needed for the degradation of muropeptides could be identified. nagZ encodes a cytosolic enzyme active on N-actylglucosamyl-beta-1,4-(1,6)-anhydromuramic acid containing muropeptides. These degradation products of the peptidoglycan are formed during the enlargement of the murein sacculus as a consequence of a growth mechanism, which couples the controlled degradation of the cell wall polymer with the insertion of new material. NagZ is needed for the formation of monosaccharides from the released disaccharides during the cytosolic steps of the muropeptide-recycling pathway. The formation of intracellular 1, 6-anhydro-N-acetylmuramyl-peptides is important for the expression control of the inducible beta-lactamases of the AmpC type. A mutant lacking active NagZ cannot establish AmpC mediated beta-lactam resistance. The biochemical characterization of the enzyme showed its activity on different muropeptides and inhibitors of enzyme activity could be identified. This observation might be important for designing inhibitors of NagZ that could prevent the establishment of beta-lactam resistance of Enterobacteria possessing inducible beta-lactamases.
Vötsch
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Max-Planck-Institut für Entwicklungsbiologie, Abteilung Biochemie, Spemannstrasse 35, 72076 Tübingen, Germany.
Templin
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MF
D000118:Acetylglucosaminidase / Q000737:chemistry* / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009154:Mutation; D010455:Peptides / Q000737:chemistry*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams
D010455:Peptides; D047090:beta-Lactams; D012965:Sodium Chloride; D000118:Acetylglucosaminidase; D001618:beta-Lactamases