2NP8

Structural Basis for the Inhibition of Aurora A Kinase by a Novel Class of High Affinity Disubstituted Pyrimidine Inhibitors

Summary for 2NP8

• Entry DOI: 10.2210/pdb2np8/pdb
• Related: 1MQ4
• Descriptor: Serine/threonine-protein kinase 6, SULFATE ION, N-{3-[(4-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}PYRIMIDIN-2-YL)AMINO]PHENYL}CYCLOPROPANECARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: aurora a kinase, aik, aurora 2 kinase, kinase, kinase inhibitor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 32045.67

Authors

Tari, L.W.,Hoffman, I.D.,Bensen, D.C.,Hunter, M.J.,Nix, J.,Nelson, K.J.,McRee, D.E.,Swanson, R.V. (deposition date: 2006-10-26, release date: 2006-12-26, Last modification date: 2023-08-30)

Primary citation

Tari, L.W.,Hoffman, I.D.,Bensen, D.C.,Hunter, M.J.,Nix, J.,Nelson, K.J.,McRee, D.E.,Swanson, R.V.
Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors.
Bioorg.Med.Chem.Lett., 17:688-691, 2007

PubMed Abstract: The 2.25 A crystal structure of a complex of Aurora A kinase (AIKA) with cyclopropanecarboxylic acid-(3-(4-(3-trifluoromethyl-phenylamino)-pyrimidin-2-ylamino)-phenyl)-amide 1 is described here. The inhibitor binding mode is novel, with the cyclopropanecarboxylic acid moiety directed towards the solvent exposed region of the ATP-binding pocket, and several induced structural changes in the active-site compared with other published AIK structures. This structure provides context for the available SAR data on this compound class, and could be exploited for the design of analogs with increased affinity and selectivity for AIK.

PubMed: 17157005
DOI: 10.1016/j.bmcl.2006.10.086

Experimental method

X-RAY DIFFRACTION (2.25 Å)