UDP-N-acetylglucosamine—peptide N-acetylglucosaminyltransferase (OGT)

UDP-N-acetylglucosamine—peptide N-acetylglucosaminyltransferase, commonly abbreviated as OGT, is a glycosyltransferase enzyme responsible for catalyzing the transfer of a single N-acetylglucosamine (GlcNAc) moiety from the nucleotide sugar donor UDP-GlcNAc to serine or threonine residues in nuclear and cytoplasmic proteins. This results in a post-translational modification known as O-GlcNAcylation. OGT glycosylates a wide range of substrates, including histones, AKT1, PFKL, TAU, and HCFC1, and thereby participates in the regulation of cellular signaling, metabolism, transcription, and apoptosis. Due to its critical involvement in the regulation of protein function and its links to cancer, neurodegeneration, and metabolic disease, OGT is considered a key therapeutic target and is under investigation for drug discovery. Its enzymatic mechanism is not fully resolved structurally, but biochemical studies support a sequential mechanism where the GlcNAc moiety is transferred to the peptide, forming O-GlcNAcylated proteins. OGT dysfunction or misregulation is associated with disrupted cell signaling and pathogenesis in numerous human diseases.

Other names

O-GlcNAc transferaseOGTO-linked N-acetylglucosaminyltransferaseUridine diphospho-N-acetylglucosamine:polypeptide N-acetylglucosaminyltransferaseBeta-N-acetylglucosaminyltransferase

Inhibition of enzymatic activity to reduce O-GlcNAc post-translational modification Modulation of protein glycosylation affecting phosphorylation and cell signaling