5UN8

Crystal Structure of human O-GlcNAcase in complex with glycopeptide p53

Summary for 5UN8

• Entry DOI: 10.2210/pdb5un8/pdb
• Related: 5UN9
• Descriptor: Protein O-GlcNAcase, P53 peptide, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: human o-glcnacase; glycopeptide, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 236960.39

Authors

Li, B.,Jiang, J. (deposition date: 2017-01-30, release date: 2017-03-15, Last modification date: 2023-10-04)

Primary citation

Li, B.,Li, H.,Lu, L.,Jiang, J.
Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.
Nat. Struct. Mol. Biol., 24:362-369, 2017

PubMed Abstract: Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes.

PubMed: 28319083
DOI: 10.1038/nsmb.3390

Experimental method

X-RAY DIFFRACTION (2.13 Å)