Issues

Intermolecular interactions of 17β-estradiol (E₂) with estrogen receptor α (ERα), of metribolone (R1881) with androgen receptor (AR), and of 17-hydroexemestane with both of these receptors. The X-ray crystal structures of E₂ (gray) and R1881 (gray) co-complexed with ERα (1GWR at 2.4 Å resolution) and AR (1XQ3 at 2.25 Å resolution), respectively, were superimposed with in silico modeled E₂ (yellow) and R1881 (yellow) docked to their cognate receptors, and compared to modeled 17-hydroexemestane (yellow) docked to ERα and AR. Hydrogen, oxygen, and nitrogen atoms are shown in cyan, red, and blue, respectively. The carbon backbone of the protein is shown in green. Hydrogens from the X-ray crystal conformations of E₂ and R1881 were omitted. H-bonds were shown to the modeled compound conformations only. Intermolecular H-bonds up to 3.5 Å are shown as black dashed lines and their length in angstroms indicated. 17-Hydroexemestane interacted with ERα as a very low affinity ligand, and with AR as a high affinity ligand, through conserved recognition motifs. For details, see Ariazi et al. in this issue.