Structural highlights
Publication Abstract from PubMed
We have modeled the ligand-binding domain (LBD) of the human estrogen receptor protein (hER) by homology to the known crystal structure of the LBD of the alpha isoform of human retinoate-X receptor (hRX). Alignment of hER with members of the nuclear receptor superfamily defined probable secondary structures which we used to constrain backbone torsion angles and hydrogen bonds. From published studies we identified key interactions between hER and estradiol to use to dock the hormone in its ligand-binding pocket. Since the hRX crystal structure corresponds to the unliganded form of the LBD, we adopted the "mousetrap" mechanism proposed by Renaud et al to predict the structure of the E2-bound hER. Refinement by molecular dynamics and energy minimization gave a model which matches well the known facts about the estradiol phamacophore. It also provides a possible explanation for how hER discriminates between estradiol and testosterone.
Homology model for the ligand-binding domain of the human estrogen receptor.,Maalouf GJ, Xu W, Smith TF, Mohr SC J Biomol Struct Dyn. 1998 Apr;15(5):841-51. PMID:9619507[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maalouf GJ, Xu W, Smith TF, Mohr SC. Homology model for the ligand-binding domain of the human estrogen receptor. J Biomol Struct Dyn. 1998 Apr;15(5):841-51. PMID:9619507
