Structural Biochemistry/Proteins/Protein O-GlcNAcylation by O-linked β-N-acetylglucosamine
β-linked N-acetylglucosamine is also known as O-GlcNAc. It is an intercellular carbohydrate that dynamiclly modifies proteins in the nucleolus and cytoplasm on the Serine and Threonine residues (Hart). The regulation of O-GlcNAc is dependent on only two enzymes OGT and O-GlcNacase (Hart). The difference between O-GlcNAc and many forms of protein glycosylation are: a.O-GlcNAcylation occurs only in the cytoplasm and nuclease b.It is not an elongated structure c.It is attached and removed several times in the life of a (Hart. It was discovered in 1983 (Hart). It is present all multicellular organisms, but not in yeast, for example, Saccharomyces cerevisiae (Hart).
O-GlcNAcylation shares more similarities to phosphoylation than other forms of protein phosphorylation. The interplay between O-GlcNAc and O-phosphate is fact, that protein phosphatase 1 catalytic subunit (PP1c). The enzyme that removes O-phosphate also regulates OGT. This suggests that the enzyme can remove the phosphate group and attach the O-GlcNAc.
The catalyst that attaches O-GlcNAc from the UDP-GlcNAc substrate to either a Serine or Theronine residue forming a β-glycosidic linkage is the O-GlcNAc tranferase(OGT) (Hart). Mammals seem to have only one gene that catalysis the OGT. There is a dependent relationship between OGT and viability of the embryonic stem cells. In the absence O-GlcNacylation in the mammalian cells is lethal (Hart). The complex regularion of OGT has not been clearly defined. But, it has been discovered that OGT is O-GlcNAcylated and phosphorylated (Hart).
Nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase) is the enzyme that removes O-GlcNAc from a protein (Hart).
1. Hart, Gerald and Akimoto, Yoshihiro. Essentials of Glycobiology. 2009.