title: Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily.
abstract: N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a cytoplasmic bifunctional enzyme involved in the biosynthesis of the nucleotide-activated UDP-GlcNAc, which is an essential precursor for the biosynthetic pathways of peptidoglycan and other components in bacteria. The crystal structure of a truncated form of GlmU has been solved at 2.25 A resolution using the multiwavelength anomalous dispersion technique and its function tested with mutagenesis studies. The molecule is composed of two distinct domains connected by a long alpha-helical arm: (i) an N-terminal domain which resembles the dinucleotide-binding Rossmann fold; and (ii) a C-terminal domain which adopts a left-handed parallel beta-helix structure (LbetaH) as found in homologous bacterial acetyltransferases. Three GlmU molecules assemble into a trimeric arrangement with tightly packed parallel LbetaH domains, the long alpha-helical linkers being seated on top of the arrangement and the N-terminal domains projected away from the 3-fold axis. In addition, the 2.3 A resolution structure of the GlmU-UDP-GlcNAc complex reveals the structural bases required for the uridyltransferase activity. These structures exemplify a three-dimensional template for the development of new antibacterial agents and for studying other members of the large family of XDP-sugar bacterial pyrophosphorylases.
authors.affiliation: AFMB-CNRS, 31 chemin Joseph Aiguier, 13402 Marseille Cedex 20.
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: F
authors.initials: F
authors.lastname: Pompeo
authors.forename: S
authors.initials: S
authors.lastname: Dixon
authors.forename: D
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.forename: C
authors.initials: C
authors.lastname: Cambillau
authors.forename: Y
authors.initials: Y
authors.lastname: Bourne
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011755:Pyrophosphatases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D000123:Acetyltransferases; D009713:Nucleotidyltransferases; C023226:UDPacetylglucosamine pyrophosphorylase; D011755:Pyrophosphatases