title: Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4.
abstract: Glycosyltransferases (GTs) catalyze the synthesis of the myriad glycoconjugates that are central to life. One of the largest families is GT4, which contains several enzymes of therapeutic significance, exemplified by WaaG and AviGT4. WaaG catalyses a key step in lipopolysaccharide synthesis, while AviGT4, produced by Streptomyces viridochromogenes, contributes to the synthesis of the antibiotic avilamycin A. Here we present the crystal structure of both WaaG and AviGT4. The two enzymes contain two "Rossmann-like" (beta/alpha/beta) domains characteristic of the GT-B fold. Both recognition of the donor substrate and the catalytic machinery is similar to other retaining GTs that display the GT-B fold. Structural information is discussed with respect to the evolution of GTs and the therapeutic significance of the two enzymes.
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5YW, United Kingdom.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez-Fleites
authors.forename: Mark
authors.initials: M
authors.lastname: Proctor
authors.forename: Shirley
authors.initials: S
authors.lastname: Roberts
authors.forename: David N
authors.initials: DN
authors.lastname: Bolam
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Gilbert
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002240:Carbohydrate Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D005964:Glucosyltransferases / Q000737:chemistry* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000096:biosynthesis; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C436977:AviG4 protein, Streptomyces viridochromogenes; D008780:Methyltransferases; D005964:Glucosyltransferases; C098465:WaaG protein, E coli; C436976:avilamycin A