4xqm

Crystal structure of the MRH domain of Glucosidase II beta bound to mannose

spinqualitylabelsall models 4xqm, resolution 1.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xqm is a 1 chain structure with sequence from Schizosaccharomyces pombe 972h-. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.625Å Ligands: MAN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLU2B_SCHPO Subunit of glucosidase 2, which cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins in the endoplasmic reticulum (ER). Specifically required for the cleavage of the final glucose. The subunit beta retains the catalytic subunit alpha in the ER. Publication Abstract from PubMed N-Glycans are modified as part of a quality control mechanism during glycoprotein folding in the endoplasmic reticulum (ER). Glucosidase II (GII) plays a critical role by generating monoglucosylated glycans that are recognized by lectin chaperones, calnexin and calreticulin. To understand how the hydrolytic activity of GIIalpha is enhanced by the mannose 6-phosphate receptor (MPR) homology domain (MRH domain) of its beta subunit, we now report a 1.6 A resolution crystal structure of the MRH domain of GIIbeta bound to mannose. A comparison of ligand-bound and unbound structures reveals no major difference in their overall fold, but rather a repositioning of side chains throughout the binding pocket, including Y372. Mutation of Y372 inhibits GII activity, demonstrating an important role for Y372 in regulating GII activity. Comparison of the MRH domains of GIIbeta, MPRs, and the ER lectin OS-9 identified conserved residues that are critical for the structural integrity and architecture of the carbohydrate binding pocket. As shown by nuclear magnetic resonance spectroscopy, mutations of the primary binding pocket residues and adjacent W409, all of which inhibit the activity of GII both in vitro and in vivo, do not cause a significant change in the overall fold of the GIIbeta MRH domain but impact locally the stability of the binding pocket. W409 does not directly contact mannose; rather, its indole ring is stabilized by binding into a hydrophobic pocket of an adjacent crystallographic neighbor. This suggests that W409 interacts with a hydrophobic region of the GIIbeta or GIIalpha subunit to modulate its effect on GII activity. Crystal Structure and Functional Analyses of the Lectin Domain of Glucosidase II: Insights into Oligomannose Recognition.,Olson LJ, Orsi R, Peterson FC, Parodi AJ, Kim JJ, D'Alessio C, Dahms NM Biochemistry. 2015 Jul 7;54(26):4097-111. doi: 10.1021/acs.biochem.5b00256. Epub , 2015 Jun 24. PMID:26062005 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Alpha-glucosidase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA