title: Structural and functional insight into human O-GlcNAcase.
abstract: O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry University of York, York, UK.
authors.forename: Christian
authors.identifier: 0000-0001-5806-0987
authors.initials: C
authors.lastname: Roth
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry University of York, York, UK.
authors.forename: Sherry
authors.initials: S
authors.lastname: Chan
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry University of York, York, UK.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Offen
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry University of York, York, UK.
authors.forename: Glyn R
authors.identifier: 0000-0002-8226-1380
authors.initials: GR
authors.lastname: Hemsworth
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Lianne I
authors.initials: LI
authors.lastname: Willems
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Dustin T
authors.initials: DT
authors.lastname: King
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Vimal
authors.initials: V
authors.lastname: Varghese
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Britton
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: David J
authors.identifier: 0000-0001-6897-5558
authors.initials: DJ
authors.lastname: Vocadlo
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry University of York, York, UK.
authors.forename: Gideon J
authors.identifier: 0000-0002-7343-776X
authors.initials: GJ
authors.lastname: Davies
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D001665:Binding Sites; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D001619:beta-N-Acetylhexosaminidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D020033:Protein Isoforms; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine