title: Molecular mechanisms of O-GlcNAcylation.
abstract: Protein glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a reversible post-translational modification of serines/threonines on metazoan proteins and occurring with similar time scales, dynamics and stoichiometry as protein phosphorylation. Levels of this modification are regulated by two enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Although the biochemistry of these enzymes and functional implications of O-GlcNAc have been studied extensively, until recently the structures and molecular mechanisms of OGT/OGA were not understood. This review covers a body of recent work that has led to an understanding of the structure of OGA, its catalytic mechanism and the development of a plethora of different inhibitors that are finding their use in cell biological studies towards the functional implications of O-GlcNAc. Furthermore, the very recent structure determination of a bacterial OGT orthologue has given the first insights into the contribution of the tetratricopeptide repeats (TPRs) to the active site and the role of some residues in catalysis and substrate binding.
authors.affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
authors.forename: Ramon
authors.initials: R
authors.lastname: Hurtado-Guerrero
authors.forename: Helge C
authors.initials: HC
authors.lastname: Dorfmueller
authors.forename: Daan M F
authors.initials: DM
authors.lastname: van Aalten
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry* / Q000378:metabolism*; D000215:Acylation; D001665:Binding Sites; D002236:Carbohydrate Conformation; D006031:Glycosylation; D054818:Hexosaminidase A / Q000737:chemistry / Q000378:metabolism; D054819:Hexosaminidase B / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational
chemical_list: D054818:Hexosaminidase A; D054819:Hexosaminidase B; D000117:Acetylglucosamine