9T4E

Human Diphosphoinositol Polyphosphate Phosphohydrolase 1 (DIPP1/NUDT3)

9T4E の概要

• エントリーDOI: 10.2210/pdb9t4e/pdb
• 分子名称: Diphosphoinositol polyphosphate phosphohydrolase 1, PHOSPHATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: inositol metabolism, phosphatase, nudix hydrolases, dipp1, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17530.70

構造登録者

Casas-Florez, D.,Marquez-Monino, M.A.,Gonzalez, B. (登録日: 2025-10-30, 公開日: 2026-06-10)

主引用文献

Casas-Florez, D.,Whitfield, H.,Perez-Canadillas, J.M.,Monterroso, B.,Riley, A.M.,Marquez-Monino, M.A.,Shipton, M.L.,Sanz-Aparicio, J.,Brearley, C.A.,Potter, B.V.L.,Gonzalez, B.
The DIPP1 family binds IP 8 in catalytically-productive twist-boat and chair conformations and associates in a ligand-dependent manner.
Int.J.Biol.Macromol., :152715-152715, 2026

PubMed Abstract: Diphosphoinositol Polyphosphate Phosphohydrolase 1 (DIPP1) is a Nudix hydrolase involved in inositol pyrophosphate (PP-InsP) metabolism, critical for cellular signaling, energy homeostasis, and stress responses. We report crystallographic and computational studies that reveal 1,5-bis-diphosphoinositol tetrakisphosphate (IP) binds to DIPP1 in two catalytically-productive inositol ring conformations. IP hydrolysis at the 1-position requires a twist-boat conformation, whereas at the 5-position a canonical chair conformation is adopted. Additionally, structural and biophysical characterization shows that the DIPP1 family undergoes ligand-sensitive changes in the association state that might be further modulated by salt concentration and/or phosphate ions. Taken together, these results advance our understanding of DIPP1 in the dynamic regulation of inositol pyrophosphate signaling networks. They provide a detailed view of DIPP1 substrate recognition and suggest oligomerization as a novel regulatory mechanism, with broader implications for phosphate sensing and functional protein-protein interactions.

PubMed: 42202926
DOI: 10.1016/j.ijbiomac.2026.152715

実験手法

X-RAY DIFFRACTION (1.541 Å)