1. Analysis of CF31 RXR-α binding.
Analysis of CF31 RXR-α binding. A, comparison of the docked conformation of CF31 (green and red) with the crystal structure of LG (yellow and red; PDB code: 3A9E). B, the interactions of LG (yellow) and CF31 (green), respectively, with the RXR-α LBP. Only residues closer than 4.2 Å to the ligand are shown (blue). Salt bridge is shown as dotted green line. The secondary structure of the RXR-α-LBD from structure of PDB 3A9E was used and specific residues of RXR-α are labeled. C, role of Arg316 mutation. CV-1 cells transiently transfected with 40 ng of pGL5-Luc reporter vector and 40 ng of Gal4-RXR-α-LBD or Gal4-RXR-α-LBD/R316A were treated with or without 9-cis-RA (10−7 mol/L) or CD3254 (10−7 mol/L) in the presence or absence of the indicated concentrations of CF31 or UVI3003. One of 3 similar experiments is shown. Bars represent means ± SEM. D, the interactions of 9-cis-RA (yellow, PDB 1FBY)) and CD3254 (black, PDB 3FUG), respectively, with Arg316 of RXR-α LBP. Comparison of ligand-residue interaction spectrum for 9-cis-RA and CF31. E, binding free energies were computed using the MM-PB/SA method, including each residue in the RXR-α LBP (from amino acids 260–450) and the overall binding free energy given by the MM-PB/SA method for 9-cis-RA and CF31.
Guang-Hui Wang et al. Cancer Res 2013;73:
©2013 by American Association for Cancer Research