+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 1l2i | ||||||
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タイトル | Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide | ||||||
要素 |
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キーワード | TRANSCRIPTION RECEPTOR/COACTIVATOR / nuclear receptor (核内受容体) / transcription factor (転写因子) / estrogen (エストロゲン) / agonist (アゴニスト) / coactivator (コアクチベーター) / TRANSCRIPTION RECEPTOR-COACTIVATOR COMPLEX | ||||||
機能・相同性 | 機能・相同性情報 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Recycling of bile acids and salts / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts / positive regulation of glucocorticoid receptor signaling pathway / Endogenous sterols / HATs acetylate histones / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 ...Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Recycling of bile acids and salts / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts / positive regulation of glucocorticoid receptor signaling pathway / Endogenous sterols / HATs acetylate histones / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 / nuclear glucocorticoid receptor binding / Estrogen-dependent gene expression / nuclear retinoic acid receptor binding / positive regulation of female receptivity / nuclear thyroid hormone receptor binding / regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / 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 / prostate epithelial cord elongation / epithelial cell development / locomotor rhythm / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / aryl hydrocarbon receptor binding / androgen metabolic process / TFIIB-class transcription factor binding / regulation of lipid metabolic process / steroid hormone mediated signaling pathway / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / positive regulation of phospholipase C activity / DNA polymerase binding / nuclear retinoid X receptor 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 / regulation of cellular response to insulin stimulus / cellular response to hormone stimulus / protein localization to chromatin / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / 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 / nuclear receptor coactivator activity / negative regulation of miRNA transcription / response to progesterone / cellular response to estradiol stimulus / transcription coregulator binding / 細胞分化 / nuclear estrogen receptor binding / nuclear receptor binding / positive regulation of nitric-oxide synthase activity / circadian regulation of gene expression / ユークロマチン / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / 概日リズム / response to estrogen / RNA polymerase II transcription regulator complex / 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 DNA-binding transcription factor activity / 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 / fibroblast proliferation / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 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 / 分子置換 / 解像度: 1.95 Å | ||||||
データ登録者 | Shiau, A.K. / Barstad, D. / Radek, J.T. / Meyers, M.J. / Nettles, K.W. / Katzenellenbogen, B.S. / Katzenellenbogen, J.A. / Agard, D.A. / Greene, G.L. | ||||||
引用 | ジャーナル: Nat.Struct.Biol. / 年: 2002 タイトル: Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. 著者: Shiau, A.K. / Barstad, D. / Radek, J.T. / Meyers, M.J. / Nettles, K.W. / Katzenellenbogen, B.S. / Katzenellenbogen, J.A. / Agard, D.A. / Greene, G.L. #1: ジャーナル: Cell(Cambridge,Mass.) / 年: 1998 タイトル: The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of this Interaction by Tamoxifen 著者: Shiau, A.K. / Barstad, D. / Loria, P.M. / Cheng, L. / Kushner, P.J. / Agard, D.A. / Greene, G.L. #2: ジャーナル: J.Med.Chem. / 年: 1999 タイトル: Estrogen Receptor Subtype-selective Ligands: Asymmetric Synthesis and Biological Evaluation of cis- and trans-5,11-dialkyl-5,6,11,12-tetrahydrochrysenes 著者: Meyers, M.J. / Sun, J. / Carlson, K.E. / Katzenellenbogen, B.S. / Katzenellenbogen, J.A. | ||||||
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 | 1l2i.cif.gz | 115.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb1l2i.ent.gz | 87.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 1l2i.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/l2/1l2i ftp://data.pdbj.org/pub/pdb/validation_reports/l2/1l2i | 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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2 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 29908.256 Da / 分子数: 2 / 断片: ligand-binding domain (residues 297-554) / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / プラスミド: pET23D / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(DE3)pLysS / 参照: UniProt: P03372 #2: タンパク質・ペプチド | 分子量: 1579.866 Da / 分子数: 2 / 断片: NR box II (residues 686-698) / 由来タイプ: 合成 詳細: The peptide was chemically synthesized. This sequence occurs naturally in mice. 参照: UniProt: Q61026 #3: 化合物 | ChemComp-CL / | #4: 化合物 | #5: 水 | ChemComp-HOH / | |
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-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 1.96 Å3/Da / 溶媒含有率: 43.48 % | |||||||||||||||||||||||||||||||||||
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結晶化 | 温度: 293 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 8.8 詳細: 16% (w/v) PEG 4000, 50 mM Magnesium chloride, 53 mM Tris pH 8.8 292-294 K, VAPOR DIFFUSION, HANGING DROP, temperature 293K | |||||||||||||||||||||||||||||||||||
結晶化 | *PLUS 温度: 19-21 ℃ | |||||||||||||||||||||||||||||||||||
溶液の組成 | *PLUS
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-データ収集
回折 | 平均測定温度: 103 K |
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放射光源 | 由来: シンクロトロン / サイト: ALS / ビームライン: 5.0.2 / 波長: 1.1 Å |
検出器 | タイプ: ADSC QUANTUM 4 / 検出器: CCD / 日付: 1999年10月24日 |
放射 | モノクロメーター: Double crystal / 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: 1.1 Å / 相対比: 1 |
反射 | 解像度: 1.95→46.8 Å / Num. all: 34533 / Num. obs: 34533 / % possible obs: 97.9 % / Observed criterion σ(I): -3 / 冗長度: 3.5 % / Biso Wilson estimate: 25.2 Å2 / Rsym value: 0.065 / Net I/σ(I): 18.8 |
反射 シェル | 解像度: 1.95→2.02 Å / Mean I/σ(I) obs: 2.9 / Num. unique all: 3432 / Rsym value: 0.531 / % possible all: 97.7 |
反射 | *PLUS Num. measured all: 119409 / Rmerge(I) obs: 0.065 |
反射 シェル | *PLUS % possible obs: 97.7 % / Rmerge(I) obs: 0.531 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: PDB ENTRY 3ERD 解像度: 1.95→46.8 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 10000 / Isotropic thermal model: Restrained / 交差検証法: THROUGHOUT / σ(F): 0 / 立体化学のターゲット値: Engh & Huber
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溶媒の処理 | 溶媒モデル: flat model / Bsol: 61.9288 Å2 / ksol: 0.360796 e/Å3 | ||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 38.53 Å2
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Refine analyze |
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精密化ステップ | サイクル: LAST / 解像度: 1.95→46.8 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 1.95→2.02 Å / Rfactor Rfree error: 0.024 / Total num. of bins used: 10
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Xplor file |
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精密化 | *PLUS Rfactor obs: 0.203 / Rfactor Rfree: 0.243 / Rfactor Rwork: 0.203 | ||||||||||||||||||||||||||||||||||||
溶媒の処理 | *PLUS | ||||||||||||||||||||||||||||||||||||
原子変位パラメータ | *PLUS | ||||||||||||||||||||||||||||||||||||
拘束条件 | *PLUS
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LS精密化 シェル | *PLUS Rfactor Rfree: 0.336 / Rfactor Rwork: 0.296 / Rfactor obs: 0.296 |