9t4c | pdb_00009t4c

Human Diphosphoinositol Polyphosphate Phosphohydrolase 1 (DIPP1) H91E mutant in complex with 1,5-(PCP)-IP5 (PCP-IP8)

spinqualitylabelsall models 9t4c, resolution 1.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9t4c is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.213Å Ligands: 4WZ, CL, MN, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NUDT3_HUMAN Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Publication Abstract from PubMed 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(8)) binds to DIPP1 in two catalytically-productive inositol ring conformations. IP(8) 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. The DIPP1 family binds IP(8) in catalytically-productive twist-boat and chair conformations and associates in a ligand-dependent manner.,Casas-Florez D, Whitfield H, Perez-Canadillas JM, Monterroso B, Riley AM, Marquez-Monino MA, Shipton ML, Sanz-Aparicio J, Brearley CA, Potter BVL, Gonzalez B Int J Biol Macromol. 2026 May 26:152715. doi: 10.1016/j.ijbiomac.2026.152715. PMID:42202926 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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