Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A (STT3A) (STT3A)

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A (STT3A) is the primary catalytic subunit of the oligosaccharyltransferase (OST) complex, an essential enzyme system located in the endoplasmic reticulum (ER) membrane (UniProt: P46977). It catalyzes the co-translational N-glycosylation of nascent polypeptides by transferring a glycan from a lipid-linked oligosaccharide to asparagine residues (PubMed: 24531325). STT3A is responsible for the majority of N-glycosylation events, which are critical for proper protein folding, stability, and trafficking. Mutations in the STT3A gene are the cause of Congenital Disorder of Glycosylation type Iy (STT3A-CDG), characterized by intellectual disability and psychomotor retardation (PubMed: 24531325). Additionally, STT3A is a crucial host factor for the replication of several flaviviruses, including Dengue and Zika viruses, which require the OST complex to glycosylate their structural proteins (PubMed: 28065601). The small molecule NGI-1 has been identified as an inhibitor of the STT3 subunits, demonstrating potential as an antiviral and anticancer agent by inducing ER stress and disrupting protein maturation (PubMed: 28065601). Despite its therapeutic potential, the essential nature of N-glycosylation in cellular physiology presents significant safety challenges for drug development targeting this enzyme.

Other names

STT3AITM1Oligosaccharyltransferase subunit STT3ASTT3-ATMCB5

Inhibition of the oligosaccharyltransferase complex catalytic activity, preventing the transfer of glycan chains to nascent proteins (PubMed: 28065601).