2QA6

Crystal Structure of Estrogen Receptor Alpha mutant 537S Complexed with 4-(6-hydroxy-1H-indazol-3-yl)benzene-1,3-diol

2QA6 の概要

• エントリーDOI: 10.2210/pdb2qa6/pdb
• 関連するPDBエントリー: 2QA8 2QAB
• 分子名称: Estrogen receptor, nuclear receptor coactivator 2, 4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: 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; Nucleus : Q8BN74
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62417.41

構造登録者

Nettles, K.W.,Bruning, J.B.,Nowak, J.,Sharma, S.K.,Hahm, J.B.,Shi, Y.,Kulp, K.,Hochberg, R.B.,Zhou, H.,Katzenellenbogen, J.A.,Katzenellenbogen, B.S.,Kim, Y.,Joachmiak, A.,Greene, G.L. (登録日: 2007-06-14, 公開日: 2008-03-18, 最終更新日: 2024-02-21)

主引用文献

Nettles, K.W.,Bruning, J.B.,Gil, G.,Nowak, J.,Sharma, S.K.,Hahm, J.B.,Kulp, K.,Hochberg, R.B.,Zhou, H.,Katzenellenbogen, J.A.,Katzenellenbogen, B.S.,Kim, Y.,Joachmiak, A.,Greene, G.L.
NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses
Nat.Chem.Biol., 4:241-247, 2008

PubMed Abstract: Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.

PubMed: 18344977
DOI: 10.1038/nchembio.76

実験手法

X-RAY DIFFRACTION (2.6 Å)