1RV1

CRYSTAL STRUCTURE OF HUMAN MDM2 WITH AN IMIDAZOLINE INHIBITOR

1RV1 の概要

• エントリーDOI: 10.2210/pdb1rv1/pdb
• 関連するPDBエントリー: 1YCR
• 分子名称: Ubiquitin-protein ligase E3 Mdm2, CIS-[4,5-BIS-(4-BROMOPHENYL)-2-(2-ETHOXY-4-METHOXYPHENYL)-4,5-DIHYDROIMIDAZOL-1-YL]-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]METHANONE (3 entities in total)
• 機能のキーワード: mdm2, p53, protein-protein interaction, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleoplasm: Q00987
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 33614.70

構造登録者

Lukacs, C.,Kammlott, U.,Graves, B. (登録日: 2003-12-12, 公開日: 2004-01-20, 最終更新日: 2023-08-23)

主引用文献

Vassilev, L.T.,Vu, B.T.,Graves, B.,Carvajal, D.,Podlaski, F.,Filipovic, Z.,Kong, N.,Kammlott, U.,Lukacs, C.,Klein, C.,Fotouhi, N.,Liu, E.A.
In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
Science, 303:844-848, 2004

PubMed Abstract: MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.

PubMed: 14704432
DOI: 10.1126/science.1092472

実験手法

X-RAY DIFFRACTION (2.3 Å)