Visualizing the reaction coordinate of an O-GlcNAc hydrolase.
N-Acetylglucosamine beta-O-linked to serine and threonine residues of nucleocytoplasmic proteins (O-GlcNAc) has been linked to neurodegeneration, cellular stress response, and transcriptional regulation. Removal of O-GlcNAc is catalyzed by O-GlcNAcase (OGA) using a substrate-assisted catalytic mechanism. Here we define the reaction coordinate using chemical approaches and directly observe both a Michaelis complex and the oxazoline intermediate.
He
Yuan
Y
York Structural Biology laboratory, Department of Chemistry, The University of York, YO10 5YW, UK.
Macauley
Matthew S
MS
Stubbs
Keith A
KA
Vocadlo
David J
DJ
Davies
Gideon J
GJ
D000117:Acetylglucosamine / Q000378:metabolism*; D055162:Biocatalysis; D004579:Electron Transport; D006801:Humans; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
D010080:Oxazoles; D006867:Hydrolases; D000117:Acetylglucosamine