5BUE
ERK2 complexed with N-benzylpyridone tetrahydroazaindazole
Summary for 5BUE
Entry DOI | 10.2210/pdb5bue/pdb |
Related | 1ERK 5BUI 5BUJ |
Descriptor | Mitogen-activated protein kinase 1, 1-benzyl-4-[3-(pyridin-4-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]pyridin-2(1H)-one, NICKEL (II) ION, ... (4 entities in total) |
Functional Keywords | erk kinase, atp inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
Biological source | Homo sapiens (Human) |
Cellular location | Cytoplasm, cytoskeleton, spindle : P28482 |
Total number of polymer chains | 1 |
Total formula weight | 41909.76 |
Authors | Bellamacina, C.R.,Shu, W.,Bussiere, D.E.,Bagdanoff, J.T. (deposition date: 2015-06-03, release date: 2015-07-15, Last modification date: 2024-03-06) |
Primary citation | Bagdanoff, J.T.,Jain, R.,Han, W.,Poon, D.,Lee, P.S.,Bellamacina, C.,Lindvall, M. Ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase. Bioorg.Med.Chem.Lett., 25:3626-3629, 2015 Cited by PubMed Abstract: A series of structure based drug design hypotheses and focused screening efforts drove improvements in the potency and lipophilic efficiency of tetrahydro-pyrazolopyridine based ERK2 inhibitors. Elaboration of a fragment chemical lead established a new lipophilic aryl-Tyr interaction resulting in a substantial potency improvement. Subsequent cleavage of the lipophilic moiety led to reconfiguration of the ligand bound binding cleft. The reconfiguration established a polar contact between a newly liberated N-H and a vicinal Asp, resulting in further improvements in lipophilic efficiency and in vitro clearance. PubMed: 26144345DOI: 10.1016/j.bmcl.2015.06.063 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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