? The N-glycosylation of membrane and secretory proteins is an essential co-translational event that occurs in all eukaryotes. N-glycosylation may affect protein conformation and function in protein sorting and targeting. Recent evidence suggests that N-glycosylation contributes to the folding process of proteins during synthesis within the ER and may participate in the formation of correct disulfide bridges. A membrane enzyme, oligosaccharyl transferase (OT), catalyzes the N-glycosylation of nascent polypeptides in the lumen of the rough ER. We propose to identify the subunit of the OT complex that recognizes and binds the active oligosaccharyl donor, GIc3Man9GIcNAc2-PP-dolichol and characterize the binding as it relates to OT function. A novel photoaffinity probe will be utilized to identify the substrate binding site of the OT complex. Knowledge of the substrate binding sites of OT will allow us to better understand the function of this ER membrane enzyme. Characterization of this key enzyme will allow us to better understand glycoprotein biosynthesis and help us design drugs and treatments to regulate this process. Future medical ramifications include targets for cell growth regulation, including the design of anticancer drugs and antibiotics. ? ? ?
| Mahajan, B; Noiva, R; Yadava, A et al. (2006) Protein disulfide isomerase assisted protein folding in malaria parasites. Int J Parasitol 36:1037-48 |
| Tian, Geng; Xiang, Song; Noiva, Robert et al. (2006) The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites. Cell 124:61-73 |
