1X7R

CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH GENISTEIN

Summary for 1X7R

• Entry DOI: 10.2210/pdb1x7r/pdb
• Related: 1U3Q 1U3R 1U3S 1U9E 1X76 1X78 1X7B 1X7J
• Descriptor: Estrogen receptor 1 (alpha), steroid receptor coactivator-3, GENISTEIN, ... (4 entities in total)
• Functional Keywords: estrogen receptor, estrogen receptor beta, er-beta, er, estrogen receptor alpha, er-alpha, estrogen, nuclear recept transcription factor, agonist, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Nucleus. Isoform 3: Nucleus: P03372
• Total number of polymer chains: 2
• Total formula weight: 29914.22

Authors

Manas, E.S.,Xu, Z.B.,Unwalla, R.J.,Somers, W.S. (deposition date: 2004-08-16, release date: 2005-03-01, Last modification date: 2024-04-03)

Primary citation

Manas, E.S.,Xu, Z.B.,Unwalla, R.J.,Somers, W.S.
Understanding the Selectivity of Genistein for Human Estrogen Receptor-Beta Using X-Ray Crystallography and Computational Methods
Structure, 12:2197-2207, 2004

PubMed Abstract: We present X-ray crystallographic and molecular modeling studies of estrogen receptors-alpha and -beta complexed with the estrogen receptor-beta-selective phytoestrogen genistein, and coactivator-derived NR box peptides containing an LXXLL motif. We demonstrate that the ligand binding mode is essentially identical when genistein is bound to both isoforms, despite the considerably weaker affinity of this ligand for estrogen receptor-alpha. In addition, we examine subtle differences between binding site residues, providing an explanation for why genistein is modestly selective for the beta isoform. To this end, we also present the results of quantum chemical studies and thermodynamic arguments that yield insight to the nature of the interactions leading to estrogen receptor-beta selectivity. The importance of our analysis to structure-based drug design is discussed.

PubMed: 15576033
DOI: 10.1016/j.str.2004.09.015

Experimental method

X-RAY DIFFRACTION (2 Å)