8g9d | pdb_00008g9d

Diphosphoinositol polyphosphate phosphohydrolase 1 (DIPP1/NUDT3) in complex with 5- phosphonodifluoroacetamide inositol pentakisphosphate (5-PCF2Am-InsP5), an analogue of 5-InsP7

spinqualitylabelsall models 8g9d, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8g9d 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 1.6Å Ligands: KDJ 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 Inositol pyrophosphates (PP-IPs) are densely phosphorylated messenger molecules involved in numerous biological processes. PP-IPs contain one or two pyrophosphate group(s) attached to a phosphorylated myo-inositol ring. 5PP-IP(5) is the most abundant PP-IP in human cells. To investigate the function and regulation by PP-IPs in biological contexts, metabolically stable analogs have been developed. Here, we report the synthesis of a new fluorinated phosphoramidite reagent and its application for the synthesis of a difluoromethylene bisphosphonate analog of 5PP-IP(5) . Subsequently, the properties of all currently reported analogs were benchmarked using a number of biophysical and biochemical methods, including co-crystallization, ITC, kinase activity assays and chromatography. Together, the results showcase how small structural alterations of the analogs can have notable effects on their properties in a biochemical setting and will guide in the choice of the most suitable analog(s) for future investigations. Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs.,Hostachy S, Wang H, Zong G, Franke K, Riley AM, Schmieder P, Potter BVL, Shears SB, Fiedler D Chemistry. 2023 Dec 1;29(67):e202302426. doi: 10.1002/chem.202302426. Epub 2023 , Oct 19. PMID:37773020 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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