+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 4k9g | ||||||
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タイトル | 1.55 A Crystal Structure of Macrophage Migration Inhibitory Factor bound to ISO-66 and a related compound | ||||||
要素 | Macrophage migration inhibitory factor | ||||||
キーワード | ISOMERASE (異性化酵素) / cytokine (サイトカイン) / secreted/endocytosed | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of prostaglandin secretion involved in immune response / positive regulation of myeloid leukocyte cytokine production involved in immune response / フェニルピルビン酸タウトメラーゼ / L-ドパクロムイソメラーゼ / dopachrome isomerase activity / phenylpyruvate tautomerase activity / positive regulation of lipopolysaccharide-mediated signaling pathway / cytokine receptor binding / positive regulation of arachidonic acid secretion / negative regulation of myeloid cell apoptotic process ...positive regulation of prostaglandin secretion involved in immune response / positive regulation of myeloid leukocyte cytokine production involved in immune response / フェニルピルビン酸タウトメラーゼ / L-ドパクロムイソメラーゼ / dopachrome isomerase activity / phenylpyruvate tautomerase activity / positive regulation of lipopolysaccharide-mediated signaling pathway / cytokine receptor binding / positive regulation of arachidonic acid secretion / negative regulation of myeloid cell apoptotic process / negative regulation of mature B cell apoptotic process / negative regulation of macrophage chemotaxis / positive regulation of chemokine (C-X-C motif) ligand 2 production / carboxylic acid metabolic process / prostaglandin biosynthetic process / negative regulation of protein metabolic process / regulation of macrophage activation / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / chemoattractant activity / positive regulation of protein kinase A signaling / protein homotrimerization / negative regulation of cellular senescence / negative regulation of DNA damage response, signal transduction by p53 class mediator / DNA damage response, signal transduction by p53 class mediator / positive regulation of B cell proliferation / positive regulation of phosphorylation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / negative regulation of cell migration / positive regulation of cytokine production / cytokine activity / Cell surface interactions at the vascular wall / positive regulation of tumor necrosis factor production / 細胞老化 / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of fibroblast proliferation / positive regulation of peptidyl-serine phosphorylation / secretory granule lumen / protease binding / vesicle / ficolin-1-rich granule lumen / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / 炎症 / negative regulation of gene expression / 自然免疫系 / Neutrophil degranulation / positive regulation of cell population proliferation / negative regulation of apoptotic process / 細胞膜 / extracellular space / extracellular exosome / extracellular region / 核質 / identical protein binding / 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 / 分子置換 / 解像度: 1.55 Å | ||||||
データ登録者 | Crichlow, G.V. / Al-Abed, Y. / Lolis, E.J. | ||||||
引用 | ジャーナル: INT J ONCOL. / 年: 2014 タイトル: ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models. 著者: Ioannou, K. / Cheng, K.F. / Crichlow, G.V. / Birmpilis, A.I. / Lolis, E.J. / Tsitsilonis, O.E. / Al-Abed, Y. | ||||||
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 | 4k9g.cif.gz | 146.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb4k9g.ent.gz | 118.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 4k9g.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/k9/4k9g ftp://data.pdbj.org/pub/pdb/validation_reports/k9/4k9g | HTTPS FTP |
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-関連構造データ
関連構造データ | 2oohS S: 精密化の開始モデル |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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単位格子 |
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非結晶学的対称性 (NCS) | NCSドメイン:
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-要素
-タンパク質 , 1種, 3分子 ABC
#1: タンパク質 | 分子量: 12355.056 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GLIF, MIF, MMIF / プラスミド: pET11b / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21(DE3) 参照: UniProt: P14174, フェニルピルビン酸タウトメラーゼ, L-ドパクロムイソメラーゼ |
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-非ポリマー , 5種, 292分子
#2: 化合物 | #3: 化合物 | ChemComp-1Q1 / | #4: 化合物 | ChemComp-CL / #5: 化合物 | ChemComp-SO4 / | #6: 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: 3.71 Å3/Da / 溶媒含有率: 66.85 % |
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結晶化 | 温度: 293 K / pH: 7.5 詳細: 1.1 mM (14 mg/ml) MIF , 10 mM inhibitor in 10% DMSO, 18 mM NaCl, 18 mM tris(hydroxymethyl)aminomethane mixed 1:1 with reservoir containing 2 M ammonium sulfate, 0.1 M tris(hydroxymethyl) ...詳細: 1.1 mM (14 mg/ml) MIF , 10 mM inhibitor in 10% DMSO, 18 mM NaCl, 18 mM tris(hydroxymethyl)aminomethane mixed 1:1 with reservoir containing 2 M ammonium sulfate, 0.1 M tris(hydroxymethyl)aminomethane, 3% isopropanol, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-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: NSLS / ビームライン: X29A / 波長: 1.0809 |
検出器 | タイプ: ADSC QUANTUM 315 / 検出器: CCD / 日付: 2007年11月17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: 1.0809 Å / 相対比: 1 |
反射 | 解像度: 1.55→110 Å / Num. obs: 79934 / % possible obs: 99.6 % / Observed criterion σ(I): -3 / 冗長度: 5.8 % / Rmerge(I) obs: 0.058 / Net I/σ(I): 23 |
反射 シェル | 解像度: 1.55→1.61 Å / 冗長度: 5.3 % / Rmerge(I) obs: 0.534 / Mean I/σ(I) obs: 2.25 / % possible all: 99.2 |
-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 2OOH 解像度: 1.55→82.76 Å / Isotropic thermal model: isotropic / 交差検証法: THROUGHOUT / σ(F): 0 / 立体化学のターゲット値: ENGH & HUBER 詳細: REFINEMENT WAS BEGUN WITH CNS. REFMAC WAS USED IN LATER STAGES. IN ACTIVE SITE A, TWO FORMS OF THE INHIBITOR (RING-OPENED AND RING-CLOSED) WERE OBSERVED. THE LOWER OCCUPANCY FORM (RING-CLOSED) ...詳細: REFINEMENT WAS BEGUN WITH CNS. REFMAC WAS USED IN LATER STAGES. IN ACTIVE SITE A, TWO FORMS OF THE INHIBITOR (RING-OPENED AND RING-CLOSED) WERE OBSERVED. THE LOWER OCCUPANCY FORM (RING-CLOSED) WAS OBSERVED IN MAPS OMITTING THIS INHIBITOR FORM WHEN CNS WAS USED FOR MAP CALCULATION, AND MISSING REFLECTIONS WERE NOT REPLACED BY FC. MAPS CALCULATED USING REFMAC, AS WELL AS CNS MAPS IN WHICH MISSING REFLECTIONS WERE REPLACED BY FC, DID NOT REVEAL THE LOWER OCCUPANCY INHIBITOR. TLS WAS USED IN LATER REFINEMENT STEPS. THE FINAL R-FACTORS LISTED TAKE THE TLS MODEL INTO ACCOUNT. WITHOUT TLS, R(OBS)=0.22629, R(WORK)=0.22590, R(FREE)=0.24575.
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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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 26.75 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
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精密化ステップ | サイクル: LAST / 解像度: 1.55→82.76 Å
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拘束条件 |
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Refine LS restraints NCS | Ens-ID: 1 / 数: 838 / Refine-ID: X-RAY DIFFRACTION
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LS精密化 シェル | 解像度: 1.55→1.59 Å
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精密化 TLS | 手法: refined / Refine-ID: X-RAY DIFFRACTION
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精密化 TLSグループ |
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