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

STT3B is one of the two catalytic subunits of the oligosaccharyltransferase (OST) complex, which facilitates the first step of N-linked glycosylation in the endoplasmic reticulum [2, 6]. While its paralog STT3A primarily mediates co-translational glycosylation, the STT3B-containing OST complex (STT3B-OST) is specialized for post-translational glycosylation, scanning for and modifying sequons that were skipped during translation or are located near the C-terminus of proteins [6, 8, 12]. This activity is vital for the proper folding and stability of various glycoproteins, including oncogenic receptors like EGFR and immune regulators like PD-L1 [5, 14]. Mutations in the STT3B gene are the primary cause of Congenital Disorder of Glycosylation type Ix (CDG1X), a multisystem disorder characterized by intellectual disability and hypotonia [1, 6]. In therapeutic development, STT3B is targeted by small molecule inhibitors like NGI-1 to disrupt cancer cell signaling and prevent viral replication, as many viruses depend on host OST machinery for the glycosylation of their envelope proteins [10, 11]. However, because N-glycosylation is an essential biological process, the development of STT3B inhibitors requires careful management of potential toxicities to ensure a viable therapeutic window [10, 11].

Other names

STT3BSTT3-BOligosaccharyltransferase complex subunit STT3BSource of immunodominant MHC-associated peptides homolog (SIMP)OSTBCDG1X

Inhibition of the catalytic activity of the oligosaccharyltransferase (OST) complex, preventing the transfer of glycans to asparagine residues on nascent or unfolded polypeptides.