5TKE

Crystal Structure of Eukaryotic Hydrolase

5TKE の概要

• エントリーDOI: 10.2210/pdb5tke/pdb
• 分子名称: O-GlcNAcase: chimera construct (2 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Isoform 3: Nucleus . Isoform 1: Cytoplasm : O60502
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 115647.13

構造登録者

Li, B.,Jiang, J. (登録日: 2016-10-06, 公開日: 2017-03-15, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.481 Å)