Modifications of the 7-Hydroxyl Group of the Transthyretin Ligand Luteolin Provide Mechanistic Insights into Its Binding Properties and High Plasma Specificity - Fig 5

Comparison between TTR-binding sites of A) 7-Cl-Lut, B) 7-MeO-Lut and C) luteolin in the dimer-dimer interface. The figures show binding of one compound in the AA’ and BB’ binding sites. The binding of 7-Cl-Lut at the AA’ and BB’ channel is coupled, i.e. if a 7-Cl-Lut ligand binds at the AA’ site with the chlorine directed down as shown in A, the 7-Cl-Lut ligand binding at the BB’ site must have an orientation so that its chlorine atom is also pointing down. For 7-MeO-Lut (B) and luteolin (C) the orientation of the ligands is not coupled. Hydrogen bonds are indicated with dotted lines. Carbon atoms from TTR and ligands are colored with blue and yellow bonds, respectively. Residue labels are only shown in A).