Structural highlights
Publication Abstract from PubMedProcessing alpha-glucosidase I (GluI) is a key member of the eukaryotic N-glycosylation processing pathway, selectively catalyzing the first glycoprotein trimming step in the endoplasmic reticulum. Inhibition of GluI activity impacts the infectivity of enveloped viruses; however, despite interest in this protein from a structural, enzymatic, and therapeutic standpoint, little is known about its structure and enzymatic mechanism in catalysis of the unique glycan substrate Glc3Man9GlcNAc2. The first structural model of eukaryotic GluI is here presented at 2-A resolution. Two catalytic residues are proposed, mutations of which result in catalytically inactive, properly folded protein. Using Autodocking methods with the known substrate and inhibitors as ligands, including a novel inhibitor characterized in this work, the active site of GluI was mapped. From these results, a model of substrate binding has been formulated, which is most likely conserved in mammalian GluI. Specificity of Processing alpha-Glucosidase I Is Guided by the Substrate Conformation: CRYSTALLOGRAPHIC AND IN SILICO STUDIES.,Barker MK, Rose DR J Biol Chem. 2013 May 10;288(19):13563-74. doi: 10.1074/jbc.M113.460436. Epub, 2013 Mar 27. PMID:23536181[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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