9T4D
Human Diphosphoinositol Polyphosphate Phosphohydrolase 1 (DIPP1) R41A mutant in complex with 5-(PP)-IP5 (5-IP7)
Summary for 9T4D
| Entry DOI | 10.2210/pdb9t4d/pdb |
| Descriptor | Diphosphoinositol polyphosphate phosphohydrolase 1, (1r,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl trihydrogen diphosphate, MAGNESIUM ION, ... (7 entities in total) |
| Functional Keywords | inositol metabolism, phosphatase, nudix hydrolases, dipp1, ip7, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 18205.85 |
| Authors | Casas-Florez, D.,Marquez-Monino, M.A.,Gonzalez, B. (deposition date: 2025-10-30, release date: 2026-06-10) |
| Primary citation | 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 Cited by 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: 42202926DOI: 10.1016/j.ijbiomac.2026.152715 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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