8V76
Crystal structure of the core catalytic domain of human inositol phosphate multikinase in complex with compound 15
Summary for 8V76
| Entry DOI | 10.2210/pdb8v76/pdb |
| Descriptor | Inositol polyphosphate multikinase, N-{(3P)-3-[(5P)-5-(2H-tetrazol-5-yl)-2,1-benzoxazol-3-yl]phenyl}cyclopentanecarboxamide, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | structure-based inhibitor development, kinase, inhibitor, inositol polyphosphate, inositol polyphosphate kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 30298.37 |
| Authors | Wang, H.,Shears, S.B. (deposition date: 2023-12-04, release date: 2024-12-11, Last modification date: 2025-12-10) |
| Primary citation | Wang, H.,Shears, S.B.,Blind, R.D. Structural Rationalization of IPMK Inhibitor Potency. J.Med.Chem., 68:24316-24325, 2025 Cited by PubMed Abstract: Inositol polyphosphate multikinase (IPMK) is a kinase linked to several cancers; recent development of a large panel of ATP-competitive inhibitors has reinvigorated enthusiasm for targeting IPMK. However, the structural basis for how these inhibitors achieve high potency is unknown. Herein, we report 14 novel cocrystal structures (1.7-2.0 resolution) of human IPMK kinase domain with these inhibitors. We also apply a radiolabeled assay and isothermal titration calorimetry that permit high-confidence IC and value determinations. The structures reveal a pocket in the ATP-binding site engaged by the most potent inhibitors. Two ordered waters also participate in hydrogen-bonding networks associated with the most potent inhibitors. In addition to providing the molecular basis for observed increases in potency and selectivity, the data presented here provide a toolbelt of 14 novel inhibitor-bound structures of human IPMK that can serve as a reference for all future IPMK structure-based inhibitor development efforts. PubMed: 41237254DOI: 10.1021/acs.jmedchem.5c02314 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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