+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 1c5x | ||||||
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タイトル | STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR | ||||||
要素 | (PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)) x 2 | ||||||
キーワード | BLOOD CLOTTING / selective / S1 site inhibitor / structure-based drug design / urokinase / trypsin / thrombin | ||||||
機能・相同性 | 機能・相同性情報 u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / regulation of signaling receptor activity / negative regulation of plasminogen activation / regulation of smooth muscle cell migration ...u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / regulation of signaling receptor activity / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / serine-type endopeptidase complex / Dissolution of Fibrin Clot / smooth muscle cell migration / plasminogen activation / regulation of cell adhesion mediated by integrin / tertiary granule membrane / negative regulation of fibrinolysis / regulation of cell adhesion / specific granule membrane / serine protease inhibitor complex / fibrinolysis / chemotaxis / blood coagulation / regulation of cell population proliferation / response to hypoxia / positive regulation of cell migration / external side of plasma membrane / serine-type endopeptidase activity / focal adhesion / Neutrophil degranulation / cell surface / signal transduction / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / DIFFERENCE FOURIER PLUS REFINEMENT / 解像度: 1.75 Å | ||||||
データ登録者 | Katz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L. | ||||||
引用 | ジャーナル: Chem.Biol. / 年: 2000 タイトル: Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. 著者: Katz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L. | ||||||
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 | 1c5x.cif.gz | 140.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb1c5x.ent.gz | 113.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 1c5x.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 | 1c5x_validation.pdf.gz | 738 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 1c5x_full_validation.pdf.gz | 749.6 KB | 表示 | |
XML形式データ | 1c5x_validation.xml.gz | 9.7 KB | 表示 | |
CIF形式データ | 1c5x_validation.cif.gz | 15.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/c5/1c5x ftp://data.pdbj.org/pub/pdb/validation_reports/c5/1c5x | 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・ペプチド | 分子量: 2708.183 Da / 分子数: 1 / 断片: SHORT CHAIN / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / プラスミド: PPIC9 / 発現宿主: Pichia pastoris (菌類) / 株 (発現宿主): HISTIDINE DEFICIENT GS115 / 参照: UniProt: P00749, u-plasminogen activator | ||||
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#2: タンパク質 | 分子量: 28435.428 Da / 分子数: 1 / 断片: CATALYTIC DOMAIN / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / プラスミド: PPIC9 / 発現宿主: Pichia pastoris (菌類) / 株 (発現宿主): HISTIDINE DEFICIENT GS115 / 参照: UniProt: P00749, u-plasminogen activator | ||||
#3: 化合物 | #4: 化合物 | ChemComp-ESI / | #5: 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: 2.01 Å3/Da / 溶媒含有率: 25.6 % | ||||||||||||||||||||||||||||||
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結晶化 | pH: 6.5 詳細: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.4, 1.4 mM 4-iodobenzo[b]thiophene-2-carboxamidine for 15 min on ice. The complex was ...詳細: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.4, 1.4 mM 4-iodobenzo[b]thiophene-2-carboxamidine for 15 min on ice. The complex was crystallized by vapor diffusion in hanging drops containing equal volumes of protein-inhibitor solution (0.28 mM uPA/A145, 1.4 mM inhibitor) and well solution (20 % 2-propanol, 20 % PEG 4K, 100 mM sodium citrate, pH 6.5) sealed over the well. | ||||||||||||||||||||||||||||||
結晶化 | *PLUS pH: 7.4 / 手法: 蒸気拡散法, ハンギングドロップ法 | ||||||||||||||||||||||||||||||
溶液の組成 | *PLUS
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-データ収集
回折 | 平均測定温度: 298 K |
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放射光源 | 由来: 回転陽極 / 波長: 1.5418 |
検出器 | タイプ: RIGAKU RAXIS IV++ / 検出器: IMAGE PLATE / 日付: 1998年3月22日 / 詳細: MSC 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: 1.32→38.49 Å / Num. all: 27491 / % possible obs: 68 % / Observed criterion σ(I): 0.8 / 冗長度: 2.8 % / Rmerge(I) obs: 0.088 / Net I/σ(I): 4 |
反射 シェル | 解像度: 1.75→1.83 Å / Rmerge(I) obs: 0.235 / Mean I/σ(I) obs: 1.6 / % possible all: 38.9 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: DIFFERENCE FOURIER PLUS REFINEMENT 開始モデル: PDB1LMW 解像度: 1.75→7.5 Å / 交差検証法: X-PLOR / σ(F): 2 詳細: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu_A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible ...詳細: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu_A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible (disordered). Residues after Glu B245 are not visible (disordered). Residues simultaneously refined in two or more conformations are: Ile_B17, Met_B47, Met_B81, Glu_B84, Glu_B86, Arg_B116, Leu_B123, Thr_B139, Arg_B166, Gln_B192, Met_B207, Lys_B223, Ser_B232, Leu_B235, part of citrate_3 No energy terms between citrate 1 and 2 are included because they appear to be hydrogen-bonded to one another via an unusually short hydrogen bond between carboxylate groups. Disordered waters are: HOH33 which is close to HOH36; HOH104 which is close to HOH107 HOH155 which is close to conformation 1 of Glu_B84 HOH283 which is close to HOH285; HOH373 which is close to HOH374; HOH715 which is close to HOH720 which is close to HOH721
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精密化ステップ | サイクル: LAST / 解像度: 1.75→7.5 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 1.75→1.83 Å / Total num. of bins used: 8
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Xplor file |
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ソフトウェア | *PLUS 名称: X-PLOR / バージョン: 3.1 / 分類: refinement | |||||||||||||||||||||||||||
精密化 | *PLUS 最低解像度: 7.5 Å / σ(F): 2 / % reflection Rfree: 10 % / Rfactor obs: 0.202 | |||||||||||||||||||||||||||
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: 0.388 / % reflection Rfree: 10 % / Rfactor Rwork: 0.322 |