Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations.

Abstract

The crystal structures of the human androgen receptor (hAR) and human progesterone receptor ligand-binding domains in complex with the same ligand metribolone (R1881) have been determined. Both three-dimensional structures show the typical nuclear receptor fold. The change of two residues in the ligand-binding pocket between the human progesterone receptor and hAR is most likely the source for the specificity of R1881 to the hAR. The structural implications of the 14 known mutations in the ligand-binding pocket of the hAR ligand-binding domains associated with either prostate cancer or the partial or complete androgen receptor insensitivity syndrome were analyzed. The effects of most of these mutants could be explained on the basis of the crystal structure.

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@article{Matas2000StructuralEF, title={Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations.}, author={Pedro Moreno Mat{\'i}as and Peter Donner and Rui Avelans Coelho and M . T . Thomaz and Cristina C Peixoto and Sofia Macedo and Norbert Otto and S Joschko and Paul Scholz and Anja Wegg and Siegfried Baesler and Myriam Schaefer and Ursula Egner and Maria Arm{\'e}nia Carrondo}, journal={The Journal of biological chemistry}, year={2000}, volume={275 34}, pages={26164-71} }