4J3E

The 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3a

4J3E の概要

• エントリーDOI: 10.2210/pdb4j3e/pdb
• 関連するPDBエントリー: 1RV1 4IPF
• 分子名称: E3 ubiquitin-protein ligase Mdm2, 4-({(4S,5R)-4,5-bis(4-chlorophenyl)-2-[4-methoxy-2-(propan-2-yloxy)phenyl]-4,5-dihydro-1H-imidazol-1-yl}carbonyl)piperazin-2-one, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mdm2, protein-protein interaction, imidazoline, ligase-antagonist complex, e3 ubiquitin ligase, p53, nucleus, ligase/antagonist
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna)
• 細胞内の位置: Nucleus, nucleoplasm (By similarity): P56273
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10640.17

構造登録者

Graves, B.J.,Lukacs, C.M.,Kammlott, R.U.,Crowther, R. (登録日: 2013-02-05, 公開日: 2013-04-24, 最終更新日: 2024-02-28)

主引用文献

Vu, B.,Wovkulich, P.,Pizzolato, G.,Lovey, A.,Ding, Q.,Jiang, N.,Liu, J.J.,Zhao, C.,Glenn, K.,Wen, Y.,Tovar, C.,Packman, K.,Vassilev, L.,Graves, B.
Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.
ACS Med Chem Lett, 4:466-469, 2013

PubMed Abstract: The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome. Many tumors produce high levels of MDM2, thereby impairing p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.

PubMed: 24900694
DOI: 10.1021/ml4000657

実験手法

X-RAY DIFFRACTION (1.91 Å)