Structural and Thermodynamic Characterization of Protein–Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors

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.