213738-28-4Relevant academic research and scientific papers
Substrate specificity of the glycosyl donor for oligosaccharyl transferase
Tai,Imperiali
, p. 6217 - 6228 (2001)
Oligosaccharyl transferase (OT) catalyzes the co-translational transfer of a dolichol-linked tetradecasaccharide (Dol-PP-GlcNAc2Man9Glc3, 1a) to an asparagine side chain of a nascent polypeptide inside the lumen of the endoplasmic reticulum (ER). The glycosyl acceptor requires an Asn-XaaThr/Ser sequon, where Xaa can be any natural amino acid except proline, for N-linked glycosylation to occur. To address the substrate specificity of the glycosyl donor, three unnatural dolichol-linked disaccharide analogues (Dol-PP-GlcNTFA-GlcNAc 1c, Dol-PP-2DFGlc-GlcNAc 1d, and Dol-PP GlcNac-Glc 1e were synthesized and evaluated as substrates or inhibitors for OT from yeast. The synthetic analogue Dol-PP-GlcNAc-Glc 1e, with substitution in the distal sugar, was found to be a substrate (Kmapp = 26 μM) for OT. On the other hand, the analogues Dol-PP-GlcNTFA-GlcNAc 1c (Ki = 154 μM) and Dol-PP-2DFGlc-GlcNAc 1d (Ki = 252 μM), with variations in the proximal sugar, were inhibitors for OT. The dolichol-linked monosaccharide Dol-PP-GlcNAc 3 was found to be the minimum unit for glycosylation to occur.
