3esw

Complex of yeast PNGase with GlcNAc2-IAc.

spinqualitylabelsall models 3esw, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3esw is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.4Å Ligands: NAG, YCM, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PNG1_YEAST Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins. Involved in the formation of free oligosaccharide in cytosol. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Peptide:N-glycanase (PNGase) is an important component of the endoplasmic reticulum-associated protein degradation pathway in which it de-glycosylates misfolded glycoproteins, thus facilitating their proteasomal degradation. PNGase belongs to the transglutaminase superfamily and features a Cys, His, and Asp catalytic triad, which is essential for its enzymatic activity. An elongated substrate-binding groove centered on the active site Cys191 was visualized in the crystal structure of apo-PNGase, whereas its complex with Z-VAD-fmk, a peptide-based inhibitor of PNGase, revealed that the inhibitor occupied one end of the substrate-binding groove while being covalently linked to the active site Cys. Recently, haloacetamidyl-containing carbohydrate-based inhibitors of PNGase were developed and shown to specifically label the active site Cys. In this study, we describe the crystal structure of yeast PNGase in complex with N,N'-diacetylchitobiose (chitobiose). We found that the chitobiose binds on the side opposite to the peptide binding site with the active site Cys191 being located approximately midway between the carbohydrate and peptide binding sites. Mutagenesis studies confirm the critical role of the chitobiose-interacting residues in substrate binding and suggest that efficient oligosaccharide binding is required for PNGase activity. In addition, the N-terminus of a symmetry-related PNGase was found to bind to the proposed peptide-binding site of PNGase. Together with the bound chitobiose, this enables us to propose a model for glycoprotein binding to PNGase. Finally, deleting the C-terminal residues of yeast PNGase, which are disordered in all structures of this enzyme, results in a significant reduction in enzyme activity, indicating that these residues might be involved in binding of the mannose residues of the glycan chain. Structural and mutational studies on the importance of oligosaccharide binding for the activity of yeast PNGase.,Zhao G, Li G, Zhou X, Matsuo I, Ito Y, Suzuki T, Lennarz WJ, Schindelin H Glycobiology. 2009 Feb;19(2):118-25. Epub 2008 Oct 14. PMID:18854368 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Peptide N-glycanase UV excision repair protein

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