5I9I

Crystal structure of LP_PLA2 in complex with Darapladib

Summary for 5I9I

• Entry DOI: 10.2210/pdb5i9i/pdb
• Related: 5I8P
• Descriptor: 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)
• Functional Keywords: lp_pla2 inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted, extracellular space: Q13093
• Total number of polymer chains: 2
• Total formula weight: 89337.30

Authors

Liu, Q.F.,Xu, Y.C. (deposition date: 2016-02-20, release date: 2016-06-15, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)