+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 1ony | ||||||
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タイトル | Oxalyl-Aryl-Amino Benzoic Acid inhibitors of PTP1B, compound 17 | ||||||
要素 | Protein-tyrosine phosphatase, non-receptor type 1 | ||||||
キーワード | HYDROLASE / Protein Tyrosine Phosphatase / oxalyl-aryl-amino benzoic acid inhibitor | ||||||
機能・相同性 | 機能・相同性情報 regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of PERK-mediated unfolded protein response / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane ...regulation of hepatocyte growth factor receptor signaling pathway / PTK6 Down-Regulation / peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity / positive regulation of receptor catabolic process / insulin receptor recycling / negative regulation of PERK-mediated unfolded protein response / negative regulation of vascular endothelial growth factor receptor signaling pathway / regulation of intracellular protein transport / IRE1-mediated unfolded protein response / cytoplasmic side of endoplasmic reticulum membrane / platelet-derived growth factor receptor-beta signaling pathway / sorting endosome / mitochondrial crista / positive regulation of IRE1-mediated unfolded protein response / regulation of type I interferon-mediated signaling pathway / regulation of endocytosis / non-membrane spanning protein tyrosine phosphatase activity / positive regulation of protein tyrosine kinase activity / peptidyl-tyrosine dephosphorylation / Regulation of IFNA/IFNB signaling / regulation of signal transduction / cellular response to unfolded protein / growth hormone receptor signaling pathway via JAK-STAT / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of signal transduction / Regulation of IFNG signaling / Growth hormone receptor signaling / MECP2 regulates neuronal receptors and channels / endoplasmic reticulum unfolded protein response / positive regulation of JUN kinase activity / Insulin receptor recycling / negative regulation of insulin receptor signaling pathway / ephrin receptor binding / Integrin signaling / protein dephosphorylation / protein-tyrosine-phosphatase / negative regulation of MAP kinase activity / protein phosphatase 2A binding / protein tyrosine phosphatase activity / endosome lumen / insulin receptor binding / Negative regulation of MET activity / negative regulation of ERK1 and ERK2 cascade / receptor tyrosine kinase binding / insulin receptor signaling pathway / actin cytoskeleton organization / early endosome / mitochondrial matrix / cadherin binding / protein kinase binding / enzyme binding / endoplasmic reticulum / protein-containing complex / RNA binding / zinc ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / 分子置換 / 解像度: 2.15 Å | ||||||
データ登録者 | Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. ...Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Mika, A.K. / Zinker, B.A. / Trevillyan, J.M. / Jirousek, M.R. | ||||||
引用 | ジャーナル: J.Med.Chem. / 年: 2003 タイトル: Discovery and Structure-Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B 著者: Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. ...著者: Liu, G. / Szczepankiewicz, B.G. / Pei, Z. / Janowich, D.A. / Xin, Z. / Hadjuk, P.J. / Abad-Zapatero, C. / Liang, H. / Hutchins, C.W. / Fesik, S.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Mika, A.K. / Zinker, B.A. / Trevillyan, J.M. / Jirousek, M.R. #1: ジャーナル: BIOORG.MED.CHEM.LETT. / 年: 2003 タイトル: Potent, Selective Inhibitors of Protein Tyrosine Phosphatase 1B 著者: Xin, Z. / Oost, T.K. / Abad-Zapatero, C. / Hajduk, P.J. / Pei, Z. / Szczepankiewicz, B.G. / Hutchins, C.W. / Ballaron, S.J. / Stashko, M.A. / Lubben, T. / Trevillyan, J.M. / Jirousek, M.R. / Liu, G. #2: ジャーナル: J.Am.Chem.Soc. / 年: 2003 タイトル: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy 著者: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. ...著者: Szczepankiewicz, B.G. / Liu, G. / Hajduk, P.J. / Abad-Zapatero, C. / Pei, Z. / Xin, Z. / Lubben, T. / Trevillyan, J.M. / Stashko, M.A. / Ballaron, S.J. / Liang, H. / Huang, F. / Hutchins, C.W. / Fesik, S.W. / Jirousek, 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 | 1ony.cif.gz | 79.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb1ony.ent.gz | 58.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 1ony.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
文書・要旨 | 1ony_validation.pdf.gz | 470.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 1ony_full_validation.pdf.gz | 475.7 KB | 表示 | |
XML形式データ | 1ony_validation.xml.gz | 8.4 KB | 表示 | |
CIF形式データ | 1ony_validation.cif.gz | 13.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/on/1ony ftp://data.pdbj.org/pub/pdb/validation_reports/on/1ony | HTTPS FTP |
-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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-要素
#1: タンパク質 | 分子量: 37365.637 Da / 分子数: 1 / 断片: PTP1B Catalytic domain / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PTPN1 OR PTP1B / プラスミド: pT7-7 / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(D33)/pTPASE 1B / 参照: UniProt: P18031, protein-tyrosine-phosphatase |
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#2: 化合物 | ChemComp-588 / |
#3: 水 | ChemComp-HOH / |
-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: 3.22 Å3/Da / 溶媒含有率: 61.83 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 7.1 詳細: Precipitation buffer: 100 mM Hepes, 0.2 M Magnesium Acetate, 14% PEG8000, pH 7.1, VAPOR DIFFUSION, HANGING DROP, temperature 277K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
結晶化 | *PLUS 温度: 4 ℃ / pH: 7.5 詳細: Puius, Y.A., (1997) Proc.Natl.Acad.Sci.USA, 94, 13420. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
溶液の組成 | *PLUS
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-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: 回転陽極 / タイプ: RIGAKU RU300 / 波長: 1.5418 Å |
検出器 | タイプ: MARRESEARCH / 検出器: CCD / 日付: 2000年8月1日 / 詳細: mirrors |
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: 1.5418 Å / 相対比: 1 |
反射 | 解像度: 2→50 Å / Num. all: 32536 / Num. obs: 30332 / % possible obs: 81.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / 冗長度: 4.8 % / Biso Wilson estimate: 33.3 Å2 / Rmerge(I) obs: 0.065 / Rsym value: 0.065 / Net I/σ(I): 16.9 |
反射 シェル | 解像度: 2→2.07 Å / 冗長度: 4.1 % / Rmerge(I) obs: 0.571 / Mean I/σ(I) obs: 2.1 / Num. unique all: 3152 / Rsym value: 0.571 / % possible all: 96.5 |
-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 1TYR and initial internal refinement 解像度: 2.15→17.44 Å / Rfactor Rfree error: 0.005 / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 2 / σ(I): 0 / 立体化学のターゲット値: Engh & Huber 詳細: Residue CYS215, listed in remark 500, corresponds to the active site CYS which is known to be in a strained conformation in this class of enzymes. Strained conformation of Gly259 is caused by ...詳細: Residue CYS215, listed in remark 500, corresponds to the active site CYS which is known to be in a strained conformation in this class of enzymes. Strained conformation of Gly259 is caused by the presence of the inhibitor in the active site and in the vicinity of Gln262.
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溶媒の処理 | 溶媒モデル: FLAT MODEL / Bsol: 73.0446 Å2 / ksol: 0.388378 e/Å3 | ||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 36.2 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: 2.15→17.44 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.15→2.23 Å / Rfactor Rfree error: 0.017 / Total num. of bins used: 10
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Xplor file |
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精密化 | *PLUS Rfactor Rfree: 0.22 | ||||||||||||||||||||||||||||||||||||
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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