title: Modeling bacterial UDP-HexNAc: polyprenol-P HexNAc-1-P transferases.
abstract: Protein N-glycosylation in eukaryotes and peptidoglycan biosynthesis in bacteria are both initiated by the transfer of a D-N-acetylhexosamine 1-phosphate to a membrane-bound polyprenol phosphate. These reactions are catalyzed by a family of transmembrane proteins known as the UDP-D-N-acetylhexosamine: polyprenol phosphate D-N-acetylhexosamine 1-phosphate transferases. The sole eukaryotic member of this family, the d-N-acetylglucosamine 1-phosphate transferase (GPT), is specific for UDP-GlcNAc as the donor substrate and uses dolichol phosphate as the membrane-bound acceptor. The bacterial translocases, MraY, WecA, and WbpL, utilize undecaprenol phosphate as the acceptor substrate, but differ in their specificity for the UDP-sugar donor substrate. The structural basis of this sugar nucleotide specificity is uncertain. However, potential carbohydrate recognition (CR) domains have been identified within the C-terminal cytoplasmic loops of MraY, WecA, and WbpL that are highly conserved in family members with the same UDP-N-acetylhexosamine specificity. This review focuses on the catalytic mechanism and substrate specificity of these bacterial UDP-D-N-acetylhexosamine: polyprenol phosphate D-N-acetylhexosamine 1-P transferases and may provide insights for the development of selective inhibitors of cell wall biosynthesis.
authors.affiliation: USDA-ARS-NCAUR, Bioproducts and Biocatalysis Research Unit, Peoria, IL, USA. pricen@ncaur.usda.gov
authors.forename: Neil P
authors.initials: NP
authors.lastname: Price
authors.forename: Frank A
authors.initials: FA
authors.lastname: Momany
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000201:enzymology; D006031:Glycosylation; D008958:Models, Molecular; D010457:Peptidoglycan / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational / Q000502:physiology; D013379:Substrate Specificity / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010457:Peptidoglycan; D017855:Transferases (Other Substituted Phosphate Groups)