+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8atr | ||||||
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タイトル | Small molecular stabilizer for C-RAF (pS259) and 14-3-3 (1075297) | ||||||
要素 |
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キーワード | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / 1080272 / covalent | ||||||
機能・相同性 | 機能・相同性情報 death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / regulation of cell motility / insulin secretion involved in cellular response to glucose stimulus / MAP kinase kinase kinase activity ...death-inducing signaling complex assembly / intermediate filament cytoskeleton organization / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / regulation of cell motility / insulin secretion involved in cellular response to glucose stimulus / MAP kinase kinase kinase activity / Negative feedback regulation of MAPK pathway / GP1b-IX-V activation signalling / IFNG signaling activates MAPKs / regulation of epidermal cell division / protein kinase C inhibitor activity / ERBB2-ERBB3 signaling pathway / regulation of cell differentiation / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / face development / pseudopodium / somatic stem cell population maintenance / thyroid gland development / neurotrophin TRK receptor signaling pathway / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / extrinsic apoptotic signaling pathway via death domain receptors / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / establishment of skin barrier / negative regulation of protein-containing complex assembly / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / Schwann cell development / type II interferon-mediated signaling pathway / activation of adenylate cyclase activity / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of stem cell proliferation / RHO GTPases activate PKNs / protein sequestering activity / protein kinase A signaling / response to muscle stretch / negative regulation of innate immune response / myelination / protein export from nucleus / CD209 (DC-SIGN) signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / insulin-like growth factor receptor signaling pathway / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / thymus development / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / RAF activation / negative regulation of protein kinase activity / wound healing / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / Stimuli-sensing channels / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of peptidyl-serine phosphorylation / MAPK cascade / Signaling by BRAF and RAF1 fusions / protein localization / insulin receptor signaling pathway / positive regulation of cell growth / regulation of apoptotic process / mitochondrial outer membrane / positive regulation of MAPK cascade / regulation of cell cycle / non-specific serine/threonine protein kinase / protein kinase activity / cadherin binding / protein phosphorylation / negative regulation of cell population proliferation / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of apoptotic process / protein kinase binding / apoptotic process / enzyme binding / negative regulation of transcription by RNA polymerase II / Golgi apparatus / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular space / extracellular exosome / ATP binding / identical protein binding 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: 1.7 Å | ||||||
データ登録者 | Visser, E.J. / Overmans, M.J.A.M. / Vandenboorn, E.M.F. / Ottmann, C. | ||||||
資金援助 | オランダ, 1件
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引用 | ジャーナル: J.Am.Chem.Soc. / 年: 2023 タイトル: Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3 sigma /ER alpha Protein-Protein Interaction from Nonselective Fragments. 著者: Konstantinidou, M. / Visser, E.J. / Vandenboorn, E. / Chen, S. / Jaishankar, P. / Overmans, M. / Dutta, S. / Neitz, R.J. / Renslo, A.R. / Ottmann, C. / Brunsveld, L. / Arkin, M.R. | ||||||
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 | 8atr.cif.gz | 72.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8atr.ent.gz | 50 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8atr.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/at/8atr ftp://data.pdbj.org/pub/pdb/validation_reports/at/8atr | HTTPS FTP |
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-関連構造データ
関連構造データ | 8ai0C 8alrC 8altC 8alvC 8alwC 8am7C 8anfC 8aoyC 8apsC 8aq1C 8aqcC 8aqeC 8aqzC 8ar4C 8ar5C 8argC 8aroC 8arqC 8arrC 8arwC 8arxC 8aryC 8arzC 8as1C 8at9C 8atpC 8atsC 8au2C 8ausC 8auyC 8av3C 8av4C 8av7C 8av8C 8awgC 8axeC 8axuC 8azeC 8b39C 3iquS S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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
-タンパク質 / タンパク質・ペプチド , 2種, 2分子 AP
#1: タンパク質 | 分子量: 26542.914 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SFN, HME1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P31947 |
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#2: タンパク質・ペプチド | 分子量: 1070.028 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) 参照: UniProt: P04049, non-specific serine/threonine protein kinase |
-非ポリマー , 4種, 271分子
#3: 化合物 | ChemComp-CL / | ||||
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#4: 化合物 | #5: 化合物 | ChemComp-O6L / | #6: 水 | ChemComp-HOH / | |
-詳細
研究の焦点であるリガンドがあるか | Y |
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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: 2.7 Å3/Da / 溶媒含有率: 54.38 % |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, シッティングドロップ法 詳細: 0.095 M HEPES (pH 7.1), PEG400 (24% (v/v)), 0.19 M CaCl2 and 5% (v/v) Glycerol |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: ESRF / ビームライン: ID23-2 / 波長: 0.87313 Å |
検出器 | タイプ: DECTRIS PILATUS 2M / 検出器: PIXEL / 日付: 2022年1月29日 |
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: 0.87313 Å / 相対比: 1 |
反射 | 解像度: 1.7→42.23 Å / Num. obs: 33236 / % possible obs: 100 % / 冗長度: 1.9 % / CC1/2: 0.998 / Net I/σ(I): 13.1 |
反射 シェル | 解像度: 1.7→1.73 Å / Num. unique obs: 1755 / CC1/2: 0.93 |
-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: 3iqu 解像度: 1.7→42.23 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.941 / SU B: 1.867 / SU ML: 0.063 / 交差検証法: THROUGHOUT / ESU R: 0.101 / ESU R Free: 0.097 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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溶媒の処理 | イオンプローブ半径: 1 Å / 減衰半径: 1 Å / VDWプローブ半径: 1.5 Å / 溶媒モデル: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 17.91 Å2
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精密化ステップ | サイクル: LAST / 解像度: 1.7→42.23 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 1.7→1.744 Å / Total num. of bins used: 20
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