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)

Summary for 4Q4C

• Entry DOI: 10.2210/pdb4q4c/pdb
• Related: 4Q4D
• Descriptor: Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2, ADENOSINE-5'-DIPHOSPHATE, (1R,3S,4R,5S,6R)-2,4,5,6-tetrakis(phosphonooxy)cyclohexane-1,3-diyl bis[trihydrogen (diphosphate)], ... (5 entities in total)
• Functional Keywords: kinase, synthesis, inositol pyrophosphate, enantiomer, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: O43314
• Total number of polymer chains: 1
• Total formula weight: 38937.61

Authors

Wang, H.,Shears, S.B. (deposition date: 2014-04-14, release date: 2014-08-06, Last modification date: 2023-09-20)

Primary citation

Capolicchio, S.,Wang, H.,Thakor, D.T.,Shears, S.B.,Jessen, H.J.
Synthesis of Densely Phosphorylated Bis-1,5-Diphospho-myo-Inositol Tetrakisphosphate and its Enantiomer by Bidirectional P-Anhydride Formation.
Angew.Chem.Int.Ed.Engl., 53:9508-9511, 2014

PubMed Abstract: 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.

PubMed: 25044992
DOI: 10.1002/anie.201404398

Experimental method

X-RAY DIFFRACTION (1.9 Å)