PDBsum entry 4j5t

Hydrolase

PDB id: 4j5t

Contents

Protein chain

788 a.a.

Ligands

NAG ×4

Waters ×285

References listed in PDB file

Key reference

• Title: Specificity of processing α-Glucosidase i is guided by the substrate conformation: crystallographic and in silico studies.
• Authors: M.K.Barker, D.R.Rose.
• Ref.: J Biol Chem, 2013, 288, 13563-13574. [DOI no: 10.1074/jbc.M113.460436]
• PubMed id: 23536181

Abstract

Processing α-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-Å 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.