A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation
Fig 13
Representative docking models.
Ugi ligand is green, other key residues—as labeled on the Fig The rest of MD-2 is yellow backbone trace with the flexible loop region shown as sticks. A) Docking mode where Ugi compound is predicted to interact with MD-2 residues Tyr131 and Phe126 (best-scored model for AZ617 docked into human receptor). B) Alternative docking mode where Ugi compound is deep inside the binding pocket away from Tyr131 and dimerization interface (best-scored model for AZ617 and the mouse receptor). C) Comparison of the docked Ugi compound and crystallographically solved Neoseptin-3 ligand in complex with the mouse receptor (model 7 from AZ161-mouse docking). MD-2 coordinates from both complexes were superimposed. AZ161—green sticks, Neoseptin-3—orange sticks.