The addition and removal of a GlcNAc moiety to serine or threonine residues of proteins (O-GlcNAc) is a common post-translational modification in multicellular eukaryotes. It occurs on hundreds of proteins in vivo, and is sometimes reciprocal with phosphorylation. Two enzymes are responsible for maintaining O-GlcNAc levels on proteins; a glycoside hydrolase (OGA) removes the sugar from a protein, and a glycosyltransferase (OGT) installs the O-GlcNAc moiety. The molecular basis for the function of O-GlcNAc in both health and disease is being decoded using genetic and chemical tools.
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