Structural and functional insight into human O-GlcNAcase

DOI: 10.1038/nchembio.2358

Authors: Christian Roth (University of York) , Sherry Chan (University of York) , Wendy A. Offen (University of York) , Glyn R. Hemsworth (University of York) , Lianne I. Willems (Simon Fraser University) , Dustin T. King (Simon Fraser University) , Vimal Varghese (Simon Fraser University) , Robert Britton (Simon Fraser University) , David J. Vocadlo (Simon Fraser University) , Gideon J. Davies (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Chemical Biology , VOL 258

State: Published (Approved)
Published: March 2017
Diamond Proposal Number(s): 1221 , 7864 , 9948

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.

Journal Keywords: Carbohydrates; Drug discovery; Enzymes; X-ray crystallography

Diamond Keywords: Alzheimer's Disease; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 06/04/2017 10:10

Discipline Tags:

Neurodegenerative Diseases Non-Communicable Diseases Health & Wellbeing Biochemistry Neurology Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)