[7][8][9][10][5][11] Other names include: Systematic name: UDP-N-α-acetyl-d-glucosamine:[protein]-3-O-N-acetyl-β-d-glucosaminyl transferase OGT catalyzes the addition of a single N-acetylglucosamine through an O-glycosidic linkage to serine or threonine and an S-glycosidic linkage to cysteine[12][13] residues of nucleocytoplasmic proteins.
[6] OGT glycosylates many proteins including: Histone H2B,[14] AKT1,[15] PFKL,[16] KMT2E/MLL5,[16] MAPT/TAU,[17] Host cell factor C1,[18] and SIN3A.
[22] OGT cleaves Host Cell Factor C1, at one or more of 6 repeating 26 amino acid sequences.
This structure supports an ordered sequential bi-bi mechanism that matches the fact that “at saturating peptide concentrations, a competitive inhibition pattern was obtained for UDP with respect to UDP-GlcNAc.”[11] The molecular mechanism of O-linked N-acetylglucosamine transferase has not been extensively studied either, since there is not a confirmed crystal structure of the enzyme.
A proposed mechanism by Lazarus et al. is supported by product inhibition patterns of UDP at saturating peptide conditions.
This mechanism proceeds with starting materials Uridine diphosphate N-acetylglucosamine, and a peptide chain with a reactive serine or threonine hydroxyl group.
UDP-5S-GlcNAc is not efficiently utilized as a donor sugar by OGT, possibly due to distortion of the pyranose ring by replacement of oxygen with sulfur.
[28] O-GlcNAc transferase is part of a dynamic competition for a serine or threonine hydroxyl functional group in a peptide unit.
[29] The post-translational modification of proteins by O-GlcNAc is spurred by glucose flux through the hexosamine biosynthetic pathway.
OGT catalyzes attachment of the O-GlcNAc group to serine and threonine, while O-GlcNAcase spurs sugar removal.
[30][31] This regulation is important for multiple cellular processes including transcription, signal transduction, and proteasomal degradation.
[20] Studies show that O-GlcNAc transferase interacts directly with the Ten eleven translocation 2 (TET2) enzyme, which converts 5-methylcytosine to 5-hydroxymethylcytosine and regulates gene transcription.
[32] Additionally, increasing levels of OGT for O-GlcNAcylation may have therapeutic effects for Alzheimer's disease patients.