Mannosyl-oligosaccharide glucosidase (MOGS) (MOGS)

Mannosyl-oligosaccharide glucosidase (MOGS), also known as glycoprotein-processing glucosidase I, is a critical enzyme located in the lumen of the endoplasmic reticulum (ER) that initiates the processing of N-linked oligosaccharides [1, 2]. It specifically catalyzes the removal of the distal alpha-1,2-linked glucose residue from the Glc3Man9GlcNAc2 precursor, which is the first step in the trimming of N-glycans after their transfer to nascent proteins [3, 4]. This enzymatic activity is essential for the subsequent interaction of glycoproteins with ER-resident chaperones, such as calnexin and calreticulin, which facilitate proper protein folding and quality control [8, 11]. Genetic deficiencies in the MOGS gene lead to a rare condition known as Congenital Disorder of Glycosylation type IIb (MOGS-CDG), characterized by multi-systemic symptoms including neurological impairment and paradoxical immune resistance to certain viruses [1, 6]. MOGS is a significant therapeutic target for broad-spectrum antiviral agents because many enveloped viruses, including HIV, Hepatitis C, and Dengue, rely on the host's glycosylation machinery for the maturation of their envelope proteins [5, 7]. Inhibitors such as celgosivir and miglustat target this enzyme to disrupt viral protein folding, thereby preventing the production of infectious virions [1, 12]. However, the clinical application of these inhibitors is often limited by gastrointestinal side effects, such as diarrhea and flatulence, caused by the off-target inhibition of intestinal alpha-glucosidases [14, 17].

Other names

Glycoprotein-processing glucosidase IGlucosidase IGCS1ER glucosidase Ialpha-Glucosidase I

Competitive inhibition of the enzyme prevents the removal of the terminal alpha-1,2-linked glucose from N-glycan precursors, leading to the accumulation of misfolded glycoproteins and their subsequent degradation via the ER-associated degradation (ERAD) pathway [1, 5, 7].