5I9I

Crystal structure of LP_PLA2 in complex with Darapladib

5I9I の概要

• エントリーDOI: 10.2210/pdb5i9i/pdb
• 関連するPDBエントリー: 5I8P
• 分子名称: Platelet-activating factor acetylhydrolase, N-[2-(diethylamino)ethyl]-2-{2-[(4-fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl}-N-{[ 4'-(trifluoromethyl)biphenyl-4-yl]methyl}acetamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: lp_pla2 inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted, extracellular space: Q13093
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89337.30

構造登録者

Liu, Q.F.,Xu, Y.C. (登録日: 2016-02-20, 公開日: 2016-06-15, 最終更新日: 2023-11-08)

主引用文献

Liu, Q.F.,Chen, X.D.,Chen, W.Y.,Yuan, X.J.,Su, H.X.,Shen, J.H.,Xu, Y.C.
Structural and Thermodynamic Characterization of Protein-Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors
J.Med.Chem., 59:5115-5120, 2016

PubMed Abstract: Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents a promising therapeutic target for atherosclerosis and Alzheimer's disease. Here we reported the first crystal structures of Lp-PLA2 bound with reversible inhibitors and the thermodynamic characterization of complexes. High rigidity of Lp-PLA2 structure and similar binding modes of inhibitors with completely different scaffolds are revealed. It not only provides the molecular basis for inhibitory activity but also sheds light on the essential features of Lp-PLA2 recognition with reversible inhibitors.

PubMed: 27078579
DOI: 10.1021/acs.jmedchem.6b00282

実験手法

X-RAY DIFFRACTION (2.7 Å)