5DGI
Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with ADP and 3,5-(PCP)2-IP4
Summary for 5DGI
| Entry DOI | 10.2210/pdb5dgi/pdb |
| Related | 5DGH |
| Descriptor | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2, ADENOSINE-5'-DIPHOSPHATE, 3,5-di-methylenebisphosphonate inositol tetrakisphosphate, ... (7 entities in total) |
| Functional Keywords | transferase inositol diphosphoinositol pentakisphosphate kinase analog methylenebisphosphonate ppip5k atp-grasp pyrophosphate diphosphate, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 39372.53 |
| Authors | Wang, H.,Shears, S.B. (deposition date: 2015-08-27, release date: 2016-08-10, Last modification date: 2023-09-27) |
| Primary citation | Hager, A.,Wu, M.,Wang, H.,Brown, N.W.,Shears, S.B.,Veiga, N.,Fiedler, D. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues. Chemistry, 22:12406-12414, 2016 Cited by PubMed Abstract: The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PubMed: 27460418DOI: 10.1002/chem.201601754 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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