title: Glucosaminylglycan biosynthesis: what we can learn from the X-ray crystal structures of glycosyltransferases GlcAT1 and EXTL2.
abstract: The X-ray crystal structures of two glycosyltransferases (GTs)--beta 1,3-glucuronyltransferase 1 (GlcAT1) and alpha 1,4-N-acetylhexosaminyltransferase (EXTL2)--have now been determined in the presence of both donor and acceptor substrates. These enzymes are involved in glucosaminylglycan (GAG) synthesis where they catalyze inverting and retaining transfer reactions, respectively. As members of a large family of enzymes that transfer sugar groups from donor nucleotide-sugars to acceptor substrates, GlcAT1 and EXTL2 retain conserved GT folds. Comparative analysis of these structures reveals signature features for selecting specific donor sugars. Adaptive binding of the disaccharide moiety of the acceptor sugars enables the enzymes to catalyze either an inverting S(N)2-type displacement reaction or a retaining S(N)i-like transfer reaction.
authors.affiliation: Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. negishi@niehs.nih.gov
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Darden
authors.forename: Lee G
authors.initials: LG
authors.lastname: Pedersen
authors.forename: Lars C
authors.initials: LC
authors.lastname: Pedersen
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006860:Hydrogen Bonding; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D006025:Glycosaminoglycans; D008565:Membrane Proteins; C110834:EXTL2 protein, human; D017351:N-Acetylglucosaminyltransferases; C067806:glucuronyltransferase GlcAT-1; D014453:Glucuronosyltransferase