Endoplasmic reticulum alpha-glucosidase I and Endoplasmic reticulum alpha-glucosidase II (ER α-glucosidase I (α-GluI), ER α-glucosidase II (α-GluII))

Endoplasmic reticulum alpha-glucosidase I and II are essential hydrolase enzymes located in the ER that mediate the sequential removal (“trimming”) of glucose residues from N-linked oligosaccharides during glycoprotein biosynthesis[1][2][5][6]. This trimming is critical for the correct folding of glycoproteins, which is monitored by the ER’s quality control system. Glucosidase I acts first by removing the terminal glucose of Glc₃Man₉GlcNAc₂, enabling subsequent trimming by glucosidase II. The correct processing of N-linked glycans is required for the functional maturation and trafficking of many secretory and membrane proteins[1][5]. Both enzymes are targets for iminosugar-based inhibitors, which block glycoprotein maturation processes and are being explored as broad-spectrum antivirals due to many viruses’ dependence on host ER glycoprotein folding[2][6]. Congenital defects in glucosidase I cause a specific type of congenital disorder of glycosylation (CDG-IIb), marked by profound immune system impacts and altered glycoprotein patterns[2]. Inhibition of ER alpha-glucosidases carries risks of toxicity, immune dysfunction, and off-target interference with normal protein maturation.

Other names

Glucosidase IGlucosidase IIα-glucosidase I (α-GluI)α-glucosidase II (α-GluII)MOGS (for glucosidase I gene)GANAB (for glucosidase II alpha subunit gene)

Inhibition blocks glucose trimming from N-glycans, leading to misfolded or improperly processed glycoproteins. Antiviral effect: Prevents correct folding of viral envelope glycoproteins, thus blocking viral replication and assembly. Protein homeostasis disruption leads to ER stress or misfolded protein degradation