Oligosaccharyltransferase complex (OST) (OST)

The Oligosaccharyltransferase (OST) complex is a multi-subunit enzyme complex embedded in the membrane of the endoplasmic reticulum (ER) that plays a central role in the N-linked glycosylation of proteins (UniProt, 2023). It catalyzes the transfer of a pre-assembled oligosaccharide (Glc3Man9GlcNAc2) from a dolichol-pyrophosphate carrier to the asparagine side chain of a nascent polypeptide as it enters the ER lumen (PubMed: 29247067). In humans, the complex is composed of several subunits, including the catalytic STT3A or STT3B proteins, which define the two major isoforms of the complex (PubMed: 30127355). Proper N-glycosylation is vital for protein folding, quality control, and cellular signaling; consequently, mutations in OST subunits are linked to Congenital Disorders of Glycosylation (CDG), which cause severe developmental and multi-organ defects (NIH: GARD). The OST complex is also a target of interest in cancer research, as many oncogenic receptors require glycosylation for activity, and in virology, as viruses like Dengue and Zika utilize the host OST for their replication cycle (PubMed: 27366451). Small molecule inhibitors such as NGI-1 have been developed to study these processes, though the fundamental necessity of glycosylation for cell survival poses a significant challenge for therapeutic window optimization (PubMed: 28847915).

Other names

Dolichyl-diphosphooligosaccharide--protein glycotransferaseOST complexN-glycosyltransferase

Inhibition of the catalytic transfer of a glycan from a dolichol-pyrophosphate donor to an asparagine residue within the Asn-X-Ser/Thr motif of a nascent polypeptide.