title: Structural investigation on WlaRG from Campylobacter jejuni: A sugar aminotransferase.
abstract: Campylobacter jejuni is a Gram-negative bacterium that represents a leading cause of human gastroenteritis worldwide. Of particular concern is the link between C. jejuni infections and the subsequent development of Guillain-Barré syndrome, an acquired autoimmune disorder leading to paralysis. All Gram-negative bacteria contain complex glycoconjugates anchored to their outer membranes, but in most strains of C. jejuni, this lipoglycan lacks the O-antigen repeating units. Recent mass spectrometry analyses indicate that the C. jejuni 81116 (Penner serotype HS:6) lipoglycan contains two dideoxyhexosamine residues, and enzymological assay data show that this bacterial strain can synthesize both dTDP-3-acetamido-3,6-dideoxy-d-glucose and dTDP-3-acetamido-3,6-dideoxy-d-galactose. The focus of this investigation is on WlaRG from C. jejuni, which plays a key role in the production of these unusual sugars by functioning as a pyridoxal 5'-phosphate dependent aminotransferase. Here, we describe the first three-dimensional structures of the enzyme in various complexes determined to resolutions of 1.7 Å or higher. Of particular significance are the external aldimine structures of WlaRG solved in the presence of either dTDP-3-amino-3,6-dideoxy-d-galactose or dTDP-3-amino-3,6-dideoxy-d-glucose. These models highlight the manner in which WlaRG can accommodate sugars with differing stereochemistries about their C-4' carbon positions. In addition, we present a corrected structure of WbpE, a related sugar aminotransferase from Pseudomonas aeruginosa, solved to 1.3 Å resolution.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706.
authors.forename: Garrett T
authors.initials: GT
authors.lastname: Dow
authors.affiliation: National Research Council Canada, Human Health Therapeutics, Ottawa, Ontario, K1A 0R6, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Gilbert
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706.
authors.forename: James B
authors.initials: JB
authors.lastname: Thoden
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Holden
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D016123:Campylobacter jejuni / Q000201:enzymology*; D000072417:Protein Domains; D000637:Transaminases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D000637:Transaminases
keywords: Campylobacter jejuni; WbpE; WlaRG; aminotransferase; dTDP-3-amino-3,6-dideoxy-d-galactose; dTDP-3-amino-3,6-dideoxy-d-glucose; lipooligosaccharide; pyridoxal 5′-phosphate