3V3B

Structure of the Stapled p53 Peptide Bound to Mdm2

3V3B の概要

• エントリーDOI: 10.2210/pdb3v3b/pdb
• 関連するPDBエントリー: 1YCR
• 関連するBIRD辞書のPRD_ID: PRD_000857
• 分子名称: E3 ubiquitin-protein ligase Mdm2, SAH-p53-8 stapled-peptide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: oncoprotein, cell cycle, dna repair, cancer, p53-derived peptide, aliphatic staple, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus, nucleoplasm: Q00987
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 25237.15

構造登録者

Baek, S.,Kutchukian, P.S.,Verdine, G.L.,Huber, R.,Holak, T.A.,Ki Won, L.,Popowicz, G.M. (登録日: 2011-12-13, 公開日: 2012-01-18, 最終更新日: 2024-10-16)

主引用文献

Baek, S.,Kutchukian, P.S.,Verdine, G.L.,Huber, R.,Holak, T.A.,Lee, K.W.,Popowicz, G.M.
Structure of the stapled p53 peptide bound to Mdm2.
J.Am.Chem.Soc., 134:103-106, 2012

PubMed Abstract: Mdm2 is a major negative regulator of the tumor suppressor p53 protein, a protein that plays a crucial role in maintaining genome integrity. Inactivation of p53 is the most prevalent defect in human cancers. Inhibitors of the Mdm2-p53 interaction that restore the functional p53 constitute potential nongenotoxic anticancer agents with a novel mode of action. We present here a 2.0 Å resolution structure of the Mdm2 protein with a bound stapled p53 peptide. Such peptides, which are conformationally and proteolytically stabilized with all-hydrocarbon staples, are an emerging class of biologics that are capable of disrupting protein-protein interactions and thus have broad therapeutic potential. The structure represents the first crystal structure of an i, i + 7 stapled peptide bound to its target and reveals that rather than acting solely as a passive conformational brace, a staple can intimately interact with the surface of a protein and augment the binding interface.

PubMed: 22148351
DOI: 10.1021/ja2090367

実験手法

X-RAY DIFFRACTION (2 Å)