9GD8

NME1 94-Diphosphoserine

これはPDB形式変換不可エントリーです。

9GD8 の概要

• エントリーDOI: 10.2210/pdb9gd8/pdb
• 関連するPDBエントリー: 9GD6 9GD9
• EMDBエントリー: 51248 51250 51251
• 分子名称: Nucleoside diphosphate kinase A (1 entity in total)
• 機能のキーワード: nucleotide kinase, post-translational modification, phosphorylation, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 109660.39

構造登録者

Roderer, D.,Schoepf, F.,Fiedler, D.,Celik, A. (登録日: 2024-08-05, 公開日: 2025-06-11, 最終更新日: 2025-11-12)

主引用文献

Celik, A.,Schopf, F.,Stieger, C.E.,Lampe, S.,Hanf, B.,Morgan, J.A.M.,Ruwolt, M.,Liu, F.,Hackenberger, C.P.R.,Roderer, D.,Fiedler, D.
Nucleoside diphosphate kinase A (NME1) catalyses its own oligophosphorylation.
Nat.Chem., 17:1757-1767, 2025

PubMed Abstract: Protein phosphorylation is a central signalling mechanism in eukaryotic cells. The scope of this post-translational modification includes protein pyro- and polyphosphorylation. Here we report the discovery of another mode of phosphorylation: protein oligophosphorylation. Using site-specifically phosphorylated and pyrophosphorylated nucleoside diphosphate kinase A (NME1), the effects of these modifications on enzyme activity were investigated. Phosphorylation, and more so pyrophosphorylation, on Thr94 reduced the nucleoside diphosphate kinase activity. Nevertheless, both phosphoprotein and pyrophosphoprotein catalysed their own oligophosphorylation-up to the formation of a hexaphosphate chain-using ATP as a cofactor. Oligophosphorylation was critically dependent on the catalytic histidine residue His118, and cryogenic electron microscopy analysis of the modified proteins suggests an intramolecular phosphoryl transfer mechanism. Oligophosphorylation of NME1 in biochemical samples, and in cell lysates, was further confirmed using mass spectrometry, and was found to promote a new set of protein interactions. Our results highlight the complex nature of phosphoregulation, and the methods described here provide the opportunity to investigate the impact of this unusual modification in the future.

PubMed: 40835738
DOI: 10.1038/s41557-025-01915-8

実験手法

ELECTRON MICROSCOPY (3.3 Å)