Figure 5

Ligand docking with the eLP domains of the IP receptor. The four residues including Gln162, Leu172, Arg173 and Met174 in the IP eLP2 (eLP1, bleu color; eLP2, red color and eLP3, yellow color) in contact with iloprost were predicted by the sequence alignment (Figure 1) using the identified four residues (Val176, Leu185, Thr186 and Leu187) in the TP eLP2 contacted with SQ29,548 (10) as a template. 3-D NMR structure of the IP receptor agonist, iloprost (42) was docked into the putative ligand recognition pocket formed by the three eLPs with respect to the contacts with Leu172, Arg1173 and Met174 in the opening of the pocket. In addition, the two residues, Ala177 and Gln178 involved in contacts with iloprost predicted by NMR spectroscopic studies (42) were also used as constraints for the iloprost docking to the recognition pocket. The configuration of the model was minimized using 1,000-step energy minimization after the iloprost was docked into the pocket. The TM domains of the IP receptor are showed with green colors.