Enzymatic basis of branching and extension of O-Man glycans for keratan sulfate biosynthesis

O-Mannose (Man) glycans are branched specifically in the brain by a dedicated glycosyltransferase, N-acetylglucosaminyltransferase IX (GnT-IX, also known as MGAT5B). Such branching of O-Man glycans was reported to be involved in diseases, including demyelination and glioma, but the enzymatic mechanisms by which O-Man glycan is specifically recognized by GnT-IX and how branched O-Man glycans are subsequently elongated by other enzymes in the brain have remained unclear. To shed light on these issues, we here first compared the structural model of GnT-IX complexed with its O-Man substrate with the crystal structure of the homologous N-glycan branching enzyme GnT-V (also known as MGAT5).