1T4E

Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor

1T4E の概要

• エントリーDOI: 10.2210/pdb1t4e/pdb
• 関連するPDBエントリー: 1RV1 1T4F 1YCR
• 分子名称: Ubiquitin-protein ligase E3 Mdm2, (4-CHLOROPHENYL)[3-(4-CHLOROPHENYL)-7-IODO-2,5-DIOXO-1,2,3,5-TETRAHYDRO-4H-1,4-BENZODIAZEPIN-4-YL]ACETIC ACID (3 entities in total)
• 機能のキーワード: mdm2-inhibitor complex, 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: 2
• 化学式量合計: 23474.48

構造登録者

Grasberger, B.L.,Schubert, C.,Koblish, H.K.,Carver, T.E.,Franks, C.F.,Zhao, S.Y.,Lu, T.,LaFrance, L.V.,Parks, D.J. (登録日: 2004-04-29, 公開日: 2005-02-08, 最終更新日: 2023-08-23)

主引用文献

Grasberger, B.L.,Lu, T.,Schubert, C.,Parks, D.J.,Carver, T.E.,Koblish, H.K.,Cummings, M.D.,LaFrance, L.V.
Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells
J.Med.Chem., 48:909-912, 2005

PubMed Abstract: HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.

PubMed: 15715460
DOI: 10.1021/jm049137g

実験手法

X-RAY DIFFRACTION (2.6 Å)