5KR9

Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with Coumestrol

5KR9 の概要

• エントリーDOI: 10.2210/pdb5kr9/pdb
• 分子名称: Estrogen receptor, NCOA2, Coumestrol, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, ligand binding, protein-ligand complex, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62469.40

構造登録者

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Nowak, J.,Kojetin, D.J.,Elemento, O.,Katzenellenbogen, J.A.,Nettles, K.W. (登録日: 2016-07-07, 公開日: 2017-02-15, 最終更新日: 2024-03-06)

主引用文献

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Nowak, J.,Wright, N.J.,Minutolo, F.,Rangarajan, E.S.,Izard, T.,Yao, X.Q.,Grant, B.J.,Kojetin, D.J.,Elemento, O.,Katzenellenbogen, J.A.,Nettles, K.W.
Systems Structural Biology Analysis of Ligand Effects on ER alpha Predicts Cellular Response to Environmental Estrogens and Anti-hormone Therapies.
Cell Chem Biol, 24:35-45, 2017

PubMed Abstract: Environmental estrogens and anti-hormone therapies for breast cancer have diverse tissue- and signaling-pathway-selective outcomes, but how estrogen receptor alpha (ERα) mediates this phenotypic diversity is poorly understood. We implemented a statistical approach to allow unbiased, parallel analyses of multiple crystal structures, and identified subtle perturbations of ERα structure by different synthetic and environmental estrogens. Many of these perturbations were in the sub-Å range, within the noise of the individual structures, but contributed significantly to the activities of synthetic and environmental estrogens. Combining structural perturbation data from many structures with quantitative cellular activity profiles of the ligands enabled identification of structural rules for ligand-specific allosteric signaling-predicting activity from structure. This approach provides a framework for understanding the diverse effects of environmental estrogens and for guiding iterative medicinal chemistry efforts to generate improved breast cancer therapies, an approach that can be applied to understanding other ligand-regulated allosteric signaling pathways.

PubMed: 28042045
DOI: 10.1016/j.chembiol.2016.11.014

実験手法

X-RAY DIFFRACTION (2.25 Å)