5TKE

Crystal Structure of Eukaryotic Hydrolase

Summary for 5TKE

• Entry DOI: 10.2210/pdb5tke/pdb
• Descriptor: O-GlcNAcase: chimera construct (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform 3: Nucleus . Isoform 1: Cytoplasm : O60502
• Total number of polymer chains: 2
• Total formula weight: 115647.13

Authors

Li, B.,Jiang, J. (deposition date: 2016-10-06, 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 (2.481 Å)