2NP8

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

2NP8 の概要

• エントリーDOI: 10.2210/pdb2np8/pdb
• 関連するPDBエントリー: 1MQ4
• 分子名称: Serine/threonine-protein kinase 6, SULFATE ION, N-{3-[(4-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}PYRIMIDIN-2-YL)AMINO]PHENYL}CYCLOPROPANECARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: aurora a kinase, aik, aurora 2 kinase, kinase, kinase inhibitor, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, centrosome: O14965
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32045.67

構造登録者

Tari, L.W.,Hoffman, I.D.,Bensen, D.C.,Hunter, M.J.,Nix, J.,Nelson, K.J.,McRee, D.E.,Swanson, R.V. (登録日: 2006-10-26, 公開日: 2006-12-26, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.25 Å)