5oxd | pdb_00005oxd

Complex of a C. perfringens O-GlcNAcase with a fragment hit

spinqualitylabelsall models 5oxd, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5oxd is a 1 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 2.6Å Ligands: B2W, CD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OGA_CLOP1 Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMed The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine and threonine residues on proteins is referred to as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) is the enzyme responsible for carrying out the modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has been implicated in a wide range of cellular processes including transcription, proteostasis, and stress response. Dysregulation of O-GlcNAc has been linked to diabetes, cancer, and neurodegenerative and cardiovascular disease. OGA has been proposed to be a drug target for the treatment of Alzheimer's and cardiovascular disease given that increased O-GlcNAc levels appear to exert a protective effect. The search for specific, potent, and drug-like OGA inhibitors with bioavailability in the brain is therefore a field of active research, requiring orthogonal high-throughput assay platforms. Here, we describe the synthesis of a novel probe for use in a fluorescence polarization based assay for the discovery of inhibitors of OGA. We show that the probe is suitable for use with both human OGA, as well as the orthologous bacterial counterpart from Clostridium perfringens, CpOGA, and the lysosomal hexosaminidases HexA/B. We structurally characterize CpOGA in complex with a ligand identified from a fragment library screen using this assay. The versatile synthesis procedure could be adapted for making fluorescent probes for the assay of other glycoside hydrolases. O-GlcNAcase Fragment Discovery with Fluorescence Polarimetry.,Borodkin VS, Rafie K, Selvan N, Aristotelous T, Navratilova I, Ferenbach AT, van Aalten DMF ACS Chem Biol. 2018 May 2. doi: 10.1021/acschembio.8b00183. PMID:29641181 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also O-GlcNAcase

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