4NJ3

Modulating the interaction between CDK2 and Cyclin A with a Quinoline-based inhibitor

4NJ3 の概要

• エントリーDOI: 10.2210/pdb4nj3/pdb
• 分子名称: Cyclin-dependent kinase 2, 6-(3-chlorophenyl)-2-{[(2S)-3-(4-hydroxyphenyl)-1-methoxy-1-oxopropan-2-yl]carbamoyl}quinoline-4-carboxylic acid (3 entities in total)
• 機能のキーワード: cell cycle, inhibition, cyclin-dependent kinase, cancer, atp-binding, cell division, mitosis, nucleotide-binding, phosphorylation, transferase, serine/threonine-protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34539.44

構造登録者

Fischmann, T.O.,Hruza, A.W. (登録日: 2013-11-08, 公開日: 2013-11-27, 最終更新日: 2024-10-30)

主引用文献

Deng, Y.,Shipps, G.W.,Zhao, L.,Siddiqui, M.A.,Popovici-Muller, J.,Curran, P.J.,Duca, J.S.,Hruza, A.W.,Fischmann, T.O.,Madison, V.S.,Zhang, R.,McNemar, C.W.,Mayhood, T.W.,Syto, R.,Annis, A.,Kirschmeier, P.,Lees, E.M.,Parry, D.A.,Windsor, W.T.
Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.
Bioorg.Med.Chem.Lett., 24:199-203, 2014

PubMed Abstract: A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.005μM.

PubMed: 24332088
DOI: 10.1016/j.bmcl.2013.11.041

実験手法

X-RAY DIFFRACTION (1.848 Å)