4CG9

Human choline kinase a1 in complex with compound 12

4CG9 の概要

• エントリーDOI: 10.2210/pdb4cg9/pdb
• 関連するPDBエントリー: 4CG8 4CGA
• 分子名称: CHOLINE KINASE ALPHA, N,N-dimethyl-1-[(4-phenylphenyl)methyl]pyridin-1-ium-4-amine (3 entities in total)
• 機能のキーワード: transferase, cancer, drug target, biscationic compounds
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: P35790
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45243.85

構造登録者

Rubio-Ruiz, B.,Figuerola-Conchas, A.,Ramos-Torrecillas, J.,Capitan-Canadas, F.,Rios-Marco, P.,Carrasco, M.P.,Gallo, M.A.,Espinosa, A.,Marco, C.,Concepcion, C.,Entrena-Guadix, A.,Hurtado-Guerrero, R.,Conejo-Garcia, A. (登録日: 2013-11-21, 公開日: 2014-01-15, 最終更新日: 2023-12-20)

主引用文献

Rubio-Ruiz, B.,Figuerola-Conchas, A.,Ramos-Torrecillas, J.,Capitan-Canadas, F.,Rios-Marco, P.,Carrasco, M.P.,Gallo, M.A.,Espinosa, A.,Marco, C.,Concepcion, C.,Entrena-Guadix, A.,Hurtado-Guerrero, R.,Conejo-Garcia, A.
Discovery of a New Binding Site on Human Choline Kinase A1: Design, Synthesis, Crystallographic Studies and Biological Evaluation of Asymmetrical Bispyridinium Derivatives
J.Med.Chem., 57:507-, 2014

PubMed Abstract: Human choline kinase α (CKα) is a validated drug target for the treatment of cancer. In recent years, a large number of CK inhibitors have been synthesized, and one of them is currently being evaluated in Phase I clinical trials as a treatment for solid tumors. Here we have evaluated a new series of asymmetrical biscationic CK inhibitors by means of enzymatic, crystallographic, and antitumor studies. We demonstrate that one of these structures adopts a completely new binding mode not observed before inducing the aperture of an adjacent binding site. This compound shows antiproliferative and apoptotic effects on cancer cells through activation of caspase-3. Therefore, this study not only provides fruitful insights into the design of more efficient compounds that may target different regions in CKα1 but also explains how these compounds induce apoptosis in cancer cells.

PubMed: 24387243
DOI: 10.1021/JM401665X

実験手法

X-RAY DIFFRACTION (1.83 Å)