Structural snapshots of the reaction coordinate for O-GlcNAc transferase

Abstract

Understanding the reaction mechanism of OGT, responsible for O-GlcNAcylating various protein substrates, has been hampered by a lack of structural information. Snapshots of ternary complexes along the reaction coordinate now provide evidence for substrate participation in an electrophilic migration mechanism. Visualization of the reaction coordinate undertaken by glycosyltransferases has remained elusive but is critical for understanding this important class of enzyme. Using substrates and substrate mimics, we describe structural snapshots of all species along the kinetic pathway for human O-linked β-N-acetylglucosamine transferase (O-GlcNAc transferase), an intracellular enzyme that catalyzes installation of a dynamic post-translational modification. The structures reveal key features of the mechanism and show that substrate participation is important during catalysis.