3K3J

P38alpha bound to novel DFG-out compound PF-00416121

Summary for 3K3J

• Entry DOI: 10.2210/pdb3k3j/pdb
• Descriptor: Mitogen-activated protein kinase 14, 2-(4-fluorophenyl)-3-oxo-6-pyridin-4-yl-N-[2-(trifluoromethyl)benzyl]-2,3-dihydropyridazine-4-carboxamide, 2-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridine, ... (4 entities in total)
• Functional Keywords: p38alpha kinase, atp-binding, kinase, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q16539
• Total number of polymer chains: 1
• Total formula weight: 42212.96

Authors

Kazmirski, S.L.,DiNitto, J.P. (deposition date: 2009-10-02, release date: 2009-11-10, Last modification date: 2024-02-21)

Primary citation

Tecle, H.,Feru, F.,Liu, H.,Kuhn, C.,Rennie, G.,Morris, M.,Shao, J.,Cheng, A.C.,Gikunju, D.,Miret, J.,Coli, R.,Xi, S.H.,Clugston, S.L.,Low, S.,Kazmirski, S.,Ding, Y.H.,Cao, Q.,Johnson, T.L.,Deshmukh, G.D.,Dinitto, J.P.,Wu, J.C.,English, J.M.
The Design, Synthesis and Potential Utility of Fluorescence Probes that Target DFG-out Conformation of p38alpha for High Throughput Screening Binding Assay.
Chem.Biol.Drug Des., 74:547-559, 2009

PubMed Abstract: The design, synthesis and utility of fluorescence probes that bind to the DFG-out conformation of p38alpha kinase are described. Probes that demonstrate good affinity for p38alpha, have been identified and one of the probes, PF-04438255, has been successfully used in an high throughput screening (HTS) assay to identify two novel non-classical p38alpha inhibitors. In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme.

PubMed: 19843080
DOI: 10.1111/j.1747-0285.2009.00884.x

Experimental method

X-RAY DIFFRACTION (1.995 Å)