4q4c

Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with ADP and synthetic 1,5-(PP)2-IP4 (1,5-IP8)

spinqualitylabelsall models 4q4c, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q4c 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 1.9Å Ligands: ADP, I8P, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VIP2_HUMAN Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at positions 1 or 3 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates at position 1 or 3 PP-InsP5, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Publication Abstract from PubMed The ubiquitous mammalian signaling molecule bis-diphosphoinositol tetrakisphosphate (1,5-(PP)2 -myo-InsP4 , or InsP8 ) displays the most congested three-dimensional array of phosphate groups found in nature. The high charge density, the accumulation of unstable P-anhydrides and P-esters, the lack of UV absorbance, and low levels of optical rotation constitute severe obstacles to its synthesis, characterization, and purification. Herein, we describe the first procedure for the synthesis of enantiopure 1,5-(PP)2 -myo-InsP4 and 3,5-(PP)2 -myo-InsP4 utilizing a C2 -symmetric P-amidite for desymmetrization and concomitant phosphitylation followed by a one-pot bidirectional P-anhydride-forming reaction that combines sixteen chemical transformations with high efficiency. The configuration of these materials is unambiguously shown by subsequent X-ray analyses of both enantiomers after being individually soaked into crystals of the kinase domain of human diphosphoinositol pentakisphosphate kinase 2. Synthesis of Densely Phosphorylated Bis-1,5-Diphospho-myo-Inositol Tetrakisphosphate and its Enantiomer by Bidirectional P-Anhydride Formation.,Capolicchio S, Wang H, Thakor DT, Shears SB, Jessen HJ Angew Chem Int Ed Engl. 2014 Jul 14. doi: 10.1002/anie.201404398. PMID:25044992 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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