Figure 1.

Schematics of ternary complex formation in hIDO1 and hTDO. (A) L-Trp oxidation reaction catalyzed by IDO and TDO. (B) View onto the ternary hTDO–O₂-L-Trp protein-ligand-substrate complex (pdb code 5TIA). hIDO1 and hTDO residues that anchor the L-Trp substrate (blue) are indicated in orange and green, respectively. (C) Ternary complex formation in hTDO requires sequential binding of the L-Trp substrate and the O₂ ligand. If O₂ binds first, the heme is oxidized and, therefore, cannot bind another O₂ ligand. Instead, it may even coordinate a substrate molecule. (D) Ternary complex formation in hIDO1 requires sequential binding of ligand and substrate. If L-Trp binds first, O₂ access to the heme iron is blocked and the ternary complex cannot form (self-inhibition).