+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5fqr | ||||||
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タイトル | Selective estrogen receptor downregulator antagonists: Tetrahydroisoquinoline phenols 2. | ||||||
要素 | ESTROGEN RECEPTORエストロゲン受容体 | ||||||
キーワード | SIGNALING PROTEIN / BREAST CANCER / ESTROGEN RECEPTOR DOWNREGULATOR / FULVESTRANT (フルベストラント) / THIQ / NUCLEAR HORMONE RECEPTOR (核内受容体) | ||||||
機能・相同性 | 機能・相同性情報 regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / epithelial cell development / prostate epithelial cord elongation / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / androgen metabolic process / TFIIB-class transcription factor binding / steroid hormone mediated signaling pathway / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / : / intracellular steroid hormone receptor signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / protein localization to chromatin / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / steroid binding / nitric-oxide synthase regulator activity / ESR-mediated signaling / 14-3-3 protein binding / transcription corepressor binding / negative regulation of miRNA transcription / cellular response to estradiol stimulus / transcription coregulator binding / 細胞分化 / nuclear estrogen receptor binding / positive regulation of nitric-oxide synthase activity / SUMOylation of intracellular receptors / ユークロマチン / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / positive regulation of DNA-binding transcription factor activity / response to estrogen / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / Regulation of RUNX2 expression and activity / nuclear receptor activity / positive regulation of nitric oxide biosynthetic process / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / sequence-specific double-stranded DNA binding / response to estradiol / PIP3 activates AKT signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / positive regulation of cytosolic calcium ion concentration / regulation of inflammatory response / fibroblast proliferation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling / calmodulin binding / DNA-binding transcription factor activity, RNA polymerase II-specific / クロマチンリモデリング / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / クロマチン / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of DNA-templated transcription / ゴルジ体 / negative regulation of transcription by RNA polymerase II / enzyme binding / シグナル伝達 / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / 核質 / 生体膜 / identical protein binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | HOMO SAPIENS (ヒト) | ||||||
手法 | X線回折 / シンクロトロン / その他 / 解像度: 1.88 Å | ||||||
データ登録者 | Scott, J.S. / Bailey, A. / Davies, R.D.M. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. ...Scott, J.S. / Bailey, A. / Davies, R.D.M. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. / Roberts, B. / Smith, P.D. | ||||||
引用 | ジャーナル: Acs Med.Chem.Lett. / 年: 2016 タイトル: Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat. 著者: Scott, J.S. / Bailey, A. / Davies, R.D. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. / Roberts, B. / Smith, P.D. #1: ジャーナル: Cancer Res. / 年: 2016 タイトル: Azd9496: An Oral Estrogen Receptor Inhibitor that Blocks the Growth of Er-Positive and Esr1-Mutant Breast Tumors in Preclinical Models. 著者: Weir, H.M. / Bradbury, R.H. / Lawson, M. / Rabow, A.A. / Buttar, D. / Callis, R.J. / Curwen, J.O. / De Almeida, C. / Ballard, P. / Hulse, M. / Donald, C.S. / Feron, L.J.L. / Karoutchi, G. / ...著者: Weir, H.M. / Bradbury, R.H. / Lawson, M. / Rabow, A.A. / Buttar, D. / Callis, R.J. / Curwen, J.O. / De Almeida, C. / Ballard, P. / Hulse, M. / Donald, C.S. / Feron, L.J.L. / Karoutchi, G. / Macfaul, P. / Moss, T. / Norman, R.A. / Pearson, S.E. / Tonge, M. / Davies, G. / Walker, G.E. / Wilson, Z. / Rowlinson, R. / Powell, S. / Sadler, C. / Richmond, G. / Ladd, B. / Pazolli, E. / Mazzola, A.M. / D'Cruz, C. / De Savi, C. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5fqr.cif.gz | 105.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5fqr.ent.gz | 82.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5fqr.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/fq/5fqr ftp://data.pdbj.org/pub/pdb/validation_reports/fq/5fqr | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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Components on special symmetry positions |
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-要素
#1: タンパク質 | 分子量: 28242.049 Da / 分子数: 1 / 断片: LIGAND-BINDING DOMAIN, UNP RESIDUES 307-554 / 変異: YES / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 発現宿主: ESCHERICHIA COLI (大腸菌) / 株 (発現宿主): BL21(DE3) / Variant (発現宿主): GOLD / 参照: UniProt: P03372 |
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#2: 化合物 | ChemComp-QHG / ( |
#3: 水 | ChemComp-HOH / |
-実験情報
-実験
実験 | 手法: X線回折 |
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-試料調製
結晶 | マシュー密度: 2.07 Å3/Da / 溶媒含有率: 40.5 % / 解説: NONE |
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結晶化 | 詳細: 0.1 M PCTP, PH 6.5 (0.04 M SODIUM PROPIONATE, 0.02 M SODIUM CACODYLATE, 0.04 M BIS-TRIS PROPANE), 22% PEG3350, 0.2M MGCL2 |
-データ収集
回折 | 平均測定温度: 100 K |
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放射光源 | 由来: シンクロトロン / サイト: Diamond / タイプ: DIAMOND / 波長: 1 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1 Å / 相対比: 1 |
反射 | 解像度: 1.9→50 Å / Num. obs: 22344 / % possible obs: 99.8 % / Observed criterion σ(I): 2 / 冗長度: 9 % / Rmerge(I) obs: 0.05 |
-解析
ソフトウェア | 名称: REFMAC / バージョン: 5.7.0032 / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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精密化 | 構造決定の手法: その他 開始モデル: NONE 解像度: 1.88→50.32 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.929 / SU B: 5.815 / SU ML: 0.088 / 交差検証法: THROUGHOUT / ESU R: 0.149 / ESU R Free: 0.134 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 30.215 Å2
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精密化ステップ | サイクル: LAST / 解像度: 1.88→50.32 Å
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拘束条件 |
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