8FE6

Crystal structure of human O-GlcNAc transferase (OGT) in complex with an exosite-binding peptide and UDP-GlcNAc

8FE6 の概要

• エントリーDOI: 10.2210/pdb8fe6/pdb
• 分子名称: UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit, A motif peptide, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE (3 entities in total)
• 機能のキーワード: o-glcnac transferase, exosite, protein-protein interaction, complex, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 332674.94

構造登録者

Xie, J.,Jiang, J. (登録日: 2022-12-05, 公開日: 2023-08-09, 最終更新日: 2023-11-08)

主引用文献

Blankenship, C.M.,Xie, J.,Benz, C.,Wang, A.,Ivarsson, Y.,Jiang, J.
Motif-dependent binding on the intervening domain regulates O-GlcNAc transferase.
Nat.Chem.Biol., 19:1423-1431, 2023

PubMed Abstract: The modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. In this study, we identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification. Using proteomic peptide phage display (ProP-PD) coupled with structural, biochemical and cellular characterizations, we discovered a strongly enriched peptide motif, employed by the Int-D to facilitate specific O-GlcNAcylation. We further show that disruption of Int-D binding dysregulates important cellular programs, including response to nutrient deprivation and glucose metabolism. These findings illustrate a mode of OGT substrate recognition and offer key insights into the biological roles of this unique domain.

PubMed: 37653170
DOI: 10.1038/s41589-023-01422-2

実験手法

X-RAY DIFFRACTION (3.06 Å)