Figure 4. Agonist SAG1.5 induced conformational changes in the ligand binding pocket.

(a) Superposition of the ligand binding pocket residues of different structures of SMO. The receptor structure and side chain carbons are shown for SMO_Anta XV (green), SMO_SANT1 (yellow), SMO_LY2940680 (salmon; PDB id: 4JKV, molecule A), and SMO_SAG1.5 (light blue) structures. The ligand SAG1.5 is shown as light blue carbons. The hydrogen bond interactions between side chains are show as dashed lines in the corresponding color of each structure. (b) A different view of the superposition of the ligand binding pocket residues. H470^6.52 which interacts with R400^5.39 in antagonist bound structures is shown. Red arrows (in (a) and (b)) are shown to indicate the conformational changes of E518^7.38 and R400^5.39 induced by SAG1.5 binding. (c) Schematic presentation of agonist induced conformation change: green is antagonist bound state, while blue is agonist bound state.