Figure 1.

The binding of IQ and DHI to the Nurr1 LBD within the “566 site” is supported by a network molecular interactions. Close-up view of Nurr1 bound (A) covalently to indolequinone in the crystal structure (PDB:6DDA), and (B) non-covalently in a computational model of the unoxidized indole, DHI. In the QM/MM model, DHI is positioned farther away from H10/11 and tilted ~45 degrees along the plane of the ring, relative to the IQ, resulting in the formation of several new intra- and intermolecular interactions. Distances ≤3.0 Å only are shown here; see Supplemental Figure 1 for additional details. In the apo LBD structure (PDB:1OVL), the guanidinium side chain of Arg563 is rotated ~180 degrees and forms an intramolecular bond with the carboxylate side chain of Glu445 (not shown).²²