Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3B (STT3B)

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3B (STT3B) is one of the two catalytic subunits of the oligosaccharyltransferase (OST) complex located in the endoplasmic reticulum (ER) membrane (UniProt P46977). While its paralog STT3A primarily mediates co-translational N-glycosylation, STT3B is specialized for post-translational glycosylation of sequons that are skipped by STT3A or located near the C-terminus of proteins (Shrimal et al., 2015, J. Cell Sci.). This function is vital for the proper folding, stability, and trafficking of a wide array of secretory and membrane proteins. Mutations in the STT3B gene lead to Congenital Disorder of Glycosylation type Ix (CDG-Ix), a condition characterized by multi-systemic defects including developmental delay and failure to thrive (NIH/GARD). In drug discovery, STT3B is a target of interest because many viral glycoproteins and oncogenic signaling receptors depend on N-glycosylation for activity. Small molecule inhibitors such as NGI-1 have been shown to target STT3B, offering a potential therapeutic avenue for treating certain cancers and viral infections by inducing ER-associated degradation of key pathogenic proteins (Lopez-Samblas et al., 2016, Nat. Chem. Biol.).

Other names

STT3BOligosaccharyltransferase subunit STT3BSTT3-BCDG1XSource of thallium resistance 3 homolog BDolichyl-diphosphooligosaccharide-protein glycosyltransferase subunit STT3B

Inhibition of the oligosaccharyltransferase (OST) complex, specifically blocking the transfer of the dolichol-linked oligosaccharide precursor to asparagine residues on nascent or newly synthesized polypeptide chains.