2j62

Structure of a bacterial O-glcnacase in complex with glcnacstatin

spinqualitylabelsall models 2j62, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2j62 is a 2 chain structure with sequence from Clostridium perfringens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: CL, GSZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OGA_CLOP1 Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. 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 Many phosphorylation signal transduction pathways in the eukaryotic cell are modulated by posttranslational modification of specific serines/threonines with N-acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate biological processes as diverse as the cell cycle, insulin signaling, and protein degradation. The two enzymes involved in this dynamic and abundant modification are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently revealed that the O-GlcNAcase possesses an active site with significant structural similarity to that of the human lysosomal hexosaminidases HexA/HexB. PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human cell lines, also inhibits these hexosaminidases. Here, we have exploited recent structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition state as revealed by X-ray crystallography. This compound is able to raise O-GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus provides a novel, potent tool for the study of the role of O-GlcNAc in intracellular signal transduction pathways. GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels.,Dorfmueller HC, Borodkin VS, Schimpl M, Shepherd SM, Shpiro NA, van Aalten DM J Am Chem Soc. 2006 Dec 27;128(51):16484-5. PMID:17177381 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hyaluronidase 3D structures O-GlcNAcase

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