4N4S
A Double Mutant Rat Erk2 in Complex With a Pyrazolo[3,4-d]pyrimidine Inhibitor
Summary for 4N4S
| Entry DOI | 10.2210/pdb4n4s/pdb |
| Descriptor | Mitogen-activated protein kinase 1, 3-[2-(benzyloxy)-8-methylquinolin-6-yl]-1-(propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total) |
| Functional Keywords | serine/threonine kinase, map kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Rattus norvegicus (rat) |
| Cellular location | Cytoplasm, cytoskeleton, spindle (By similarity): P63086 |
| Total number of polymer chains | 2 |
| Total formula weight | 83556.00 |
| Authors | Hari, S.B.,Maly, D.J.,Merritt, E.A. (deposition date: 2013-10-08, release date: 2014-04-16, Last modification date: 2023-09-20) |
| Primary citation | Hari, S.B.,Merritt, E.A.,Maly, D.J. Conformation-Selective ATP-Competitive Inhibitors Control Regulatory Interactions and Noncatalytic Functions of Mitogen-Activated Protein Kinases. Chem.Biol., 21:628-635, 2014 Cited by PubMed Abstract: Most potent protein kinase inhibitors act by competing with ATP to block the phosphotransferase activity of their targets. However, emerging evidence demonstrates that ATP-competitive inhibitors can affect kinase interactions and functions in ways beyond blocking catalytic activity. Here, we show that stabilizing alternative ATP-binding site conformations of the mitogen-activated protein kinases (MAPKs) p38α and Erk2 with ATP-competitive inhibitors differentially, and in some cases divergently, modulates the abilities of these kinases to interact with upstream activators and deactivating phosphatases. Conformation-selective ligands are also able to modulate Erk2's ability to allosterically activate the MAPK phosphatase DUSP6, highlighting how ATP-competitive ligands can control noncatalytic kinase functions. Overall, these studies underscore the relationship between the ATP-binding and regulatory sites of MAPKs and provide insight into how ATP-competitive ligands can be designed to confer graded control over protein kinase function. PubMed: 24704509DOI: 10.1016/j.chembiol.2014.02.016 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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