3D83

Crystal structure of P38 kinase in complex with a biphenyl amide inhibitor

Summary for 3D83

• Entry DOI: 10.2210/pdb3d83/pdb
• Related: 2ZB0 2ZB1 3D7Z
• Descriptor: Mitogen-activated protein kinase 14, N-{4'-[(cyclopropylmethyl)carbamoyl]-6-methylbiphenyl-3-yl}-2-morpholin-4-ylpyridine-4-carboxamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: p38, serine/threonine protein kinase, map kinase, atp-binding, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens
• Cellular location: Cytoplasm : Q16539
• Total number of polymer chains: 1
• Total formula weight: 41937.85

Authors

Somers, D.O. (deposition date: 2008-05-22, release date: 2008-07-22, Last modification date: 2024-10-30)

Primary citation

Angell, R.M.,Angell, T.D.,Bamborough, P.,Bamford, M.J.,Chung, C.W.,Cockerill, S.G.,Flack, S.S.,Jones, K.L.,Laine, D.I.,Longstaff, T.,Ludbrook, S.,Pearson, R.,Smith, K.J.,Smee, P.A.,Somers, D.O.,Walker, A.L.
Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes.
Bioorg.Med.Chem.Lett., 18:4433-4437, 2008

PubMed Abstract: The biphenyl amides (BPAs) are a series of p38alpha MAP kinase inhibitors. Compounds are able to bind to the kinase in either the DFG-in or DFG-out conformation, depending on substituents. X-ray, binding, kinetic and cellular data are shown, providing the most detailed comparison to date between potent compounds from the same chemical series that bind to different p38alpha conformations. DFG-out-binding compounds could be made more potent than DFG-in-binding compounds by increasing their size. Unexpectedly, compounds that bound to the DGF-out conformation showed diminished selectivity. The kinetics of binding to the isolated enzyme and the effects of compounds on cells were largely unaffected by the kinase conformation bound.

PubMed: 18602262
DOI: 10.1016/j.bmcl.2008.06.028

Experimental method

X-RAY DIFFRACTION (1.9 Å)