3LBJ
Structure of human MDMX protein in complex with a small molecule inhibitor
3LBJ の概要
エントリーDOI | 10.2210/pdb3lbj/pdb |
関連するPDBエントリー | 3DAB 3LBK 3LBL |
分子名称 | Protein Mdm4, N-[(3S)-1-({6-chloro-3-[1-(4-chlorobenzyl)-4-phenyl-1H-imidazol-5-yl]-1H-indol-2-yl}carbonyl)pyrrolidin-3-yl]-N,N',N'-trimethylpropane-1,3-diamine, SULFATE ION, ... (4 entities in total) |
機能のキーワード | mdmx, mdm2, p53, inhibitor, alternative splicing, nucleus, polymorphism, zinc-finger, cell cycle |
由来する生物種 | Homo sapiens (human) |
タンパク質・核酸の鎖数 | 1 |
化学式量合計 | 11647.40 |
構造登録者 | Popowicz, G.M.,Czarna, A.,Wolf, S.,Holak, T.A. (登録日: 2010-01-08, 公開日: 2010-03-16, 最終更新日: 2023-11-01) |
主引用文献 | Popowicz, G.M.,Czarna, A.,Wolf, S.,Wang, K.,Wang, W.,Domling, A.,Holak, T.A. Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery Cell Cycle, 9:1104-1111, 2010 Cited by PubMed Abstract: Intensive anticancer drug discovery efforts have been made to develop small molecule inhibitors of the p53-MDM2 and p53-MDMX interactions. We present here the structures of the most potent inhibitors bound to MDM2 and MDMX that are based on the new imidazo-indole scaffold. In addition, the structure of the recently reported spiro-oxindole inhibitor bound to MDM2 is described. The structures indicate how the substituents of a small molecule that bind to the three subpockets of the MDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX. While the spiro-oxindole inhibitor triggers significant ligand-induced changes in MDM2, the imidazo-indoles share similar binding modes for MDMX and MDM2, but cause only minimal induced-fit changes in the structures of both proteins. Our study includes the first structure of the complex between MDMX and a small molecule and should aid in developing efficient scaffolds for binding to MDMX and/or MDM2. PubMed: 20237429DOI: 10.4161/cc.9.6.10956 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.5 Å) |
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