Structural and functional insight into human O-GlcNAcase

March 27th, 2017 by Christian Roth

Nature Chemical Biology 13, 610 (2017). doi:10.1038/nchembio.2358

Authors: Christian Roth, Sherry Chan, Wendy A Offen, Glyn R Hemsworth, Lianne I Willems, Dustin T King, Vimal Varghese, Robert Britton, David J Vocadlo & Gideon J Davies

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.