title: Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases.
abstract: MurG is an essential glycosyltransferase that forms the glycosidic linkage between N-acetyl muramyl pentapeptide and N-acetyl glucosamine in the biosynthesis of the bacterial cell wall. This enzyme is a member of a major superfamily of NDP-glycosyltransferases for which no x-ray structures containing intact substrates have been reported. Here we present the 2.5-A crystal structure of Escherichia coli MurG in complex with its donor substrate, UDP-GlcNAc. Combined with genomic analysis of other superfamily members and site-specific mutagenesis of E. coli MurG, this structure sheds light on the molecular basis for both donor and acceptor selectivity for the superfamily. This structural analysis suggests that it will be possible to evolve new glycosyltransferases from prototypical superfamily members by varying two key loops while maintaining the overall architecture of the family and preserving key residues.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ 08540, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Hu
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Sha
authors.initials: S
authors.lastname: Ha
authors.forename: Ben
authors.initials: B
authors.lastname: Gross
authors.forename: Brian
authors.initials: B
authors.lastname: Falcone
authors.forename: Deborah
authors.initials: D
authors.lastname: Walker
authors.forename: Maryam
authors.initials: M
authors.lastname: Mokhtarzadeh
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D014537:Uridine Diphosphate N-Acetylglucosamine; D017351:N-Acetylglucosaminyltransferases; C064057:UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase