2cbj | pdb_00002cbj

Structure of the Clostridium perfringens NagJ family 84 glycoside hydrolase, a homologue of human O-GlcNAcase in complex with PUGNAc

spinqualitylabelsall models 2cbj, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2cbj is a 2 chain structure with sequence from "bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898. The September 2011 RCSB PDB Molecule of the Month feature on O-GlcNAc Transferase by David Goodsell is 10.2210/rcsb_pdb/mom_2011_9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, OAN Related: 2cbi Activity: Hydrolase, with EC number 3.2.1.35 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [OGA_CLOPE] Binds carbohydrates. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Can bind and deglycosylate O-glycosylated peptides from mammals. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates (in vitro).[UniProtKB:Q0TR53] 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 O-linked N-acetylglucosamine (O-GlcNAc) modification of specific serines/threonines on intracellular proteins in higher eukaryotes has been shown to directly regulate important processes such as the cell cycle, insulin sensitivity and transcription. The structure, molecular mechanisms of catalysis, protein substrate recognition/specificity of the eukaryotic O-GlcNAc transferase and hydrolase are largely unknown. Here we describe the crystal structure, enzymology and in vitro activity on human substrates of Clostridium perfringens NagJ, a close homologue of human O-GlcNAcase (OGA), representing the first family 84 glycoside hydrolase structure. The structure reveals a deep active site pocket highly conserved with the human enzyme, compatible with binding of O-GlcNAcylated peptides. Together with mutagenesis data, the structure supports a variant of the substrate-assisted catalytic mechanism, involving two aspartic acids and an unusually positioned tyrosine. Insights into recognition of substrate come from a complex with the transition state mimic O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (Ki=5.4 nM). Strikingly, the enzyme is inhibited by the pseudosubstrate peptide Ala-Cys(-S-GlcNAc)-Ala, and has OGA activity against O-GlcNAcylated human proteins, suggesting that the enzyme is a suitable model for further studies into the function of human OGA. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis.,Rao FV, Dorfmueller HC, Villa F, Allwood M, Eggleston IM, van Aalten DM EMBO J. 2006 Apr 5;25(7):1569-78. Epub 2006 Mar 16. PMID:16541109 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hyaluronidase 3D structures

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