+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 2orr | ||||||
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タイトル | Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 4-(Benzo[1,3]dioxol-5-yloxy)-2-(4-imidazol-1-yl-phenoxy)-pyrimidine Complex | ||||||
要素 | Nitric oxide synthase, inducible一酸化窒素合成酵素 | ||||||
キーワード | OXIDOREDUCTASE (酸化還元酵素) / NITRIC OXIDE (一酸化窒素) / L-ARGININE MONOOXYGENASE / HEME (ヘム) / DIMERIZATION / INHIBITOR (酵素阻害剤) / NOS | ||||||
機能・相同性 | 機能・相同性情報 Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / prostaglandin secretion / positive regulation of killing of cells of another organism / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton ...Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / prostaglandin secretion / positive regulation of killing of cells of another organism / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton / superoxide metabolic process / cGMP-mediated signaling / nitric-oxide synthase binding / cellular response to cytokine stimulus / regulation of cytokine production involved in inflammatory response / peptidyl-cysteine S-nitrosylation / regulation of insulin secretion / cellular response to organic cyclic compound / nitric-oxide synthase (NADPH) / blood vessel remodeling / response to tumor necrosis factor / nitric-oxide synthase activity / nitric oxide mediated signal transduction / arginine catabolic process / nitric oxide biosynthetic process / negative regulation of blood pressure / response to hormone / positive regulation of interleukin-8 production / response to bacterium / Hsp90 protein binding / negative regulation of protein catabolic process / beta-catenin binding / 血圧 / cellular response to type II interferon / positive regulation of interleukin-6 production / ペルオキシソーム / 概日リズム / cellular response to xenobiotic stimulus / FMN binding / flavin adenine dinucleotide binding / NADP binding / actin binding / regulation of cell population proliferation / cellular response to lipopolysaccharide / response to lipopolysaccharide / response to hypoxia / calmodulin binding / intracellular signal transduction / defense response to bacterium / cadherin binding / 炎症 / positive regulation of apoptotic process / negative regulation of gene expression / heme binding / protein kinase binding / perinuclear region of cytoplasm / protein homodimerization activity / extracellular space / identical protein binding / metal ion binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||
手法 | X線回折 / シンクロトロン / フーリエ合成 / 解像度: 2 Å | ||||||
データ登録者 | Adler, M. / Whitlow, M. | ||||||
引用 | ジャーナル: J.Med.Chem. / 年: 2007 タイトル: Design, Synthesis, and Activity of 2-Imidazol-1-ylpyrimidine Derived Inducible Nitric Oxide Synthase Dimerization Inhibitors 著者: Davey, D.D. / Adler, M. / Arnaia, D. / Eagen, K. / Erickson, S. / Guilford, W. / Kenrick, M. / Morrissey, M.M. / Ohimeyer, M. / Pan, G. / Paradkar, V.M. / Parkinson, J. / Polokoff, M. / ...著者: Davey, D.D. / Adler, M. / Arnaia, D. / Eagen, K. / Erickson, S. / Guilford, W. / Kenrick, M. / Morrissey, M.M. / Ohimeyer, M. / Pan, G. / Paradkar, V.M. / Parkinson, J. / Polokoff, M. / Salonz, K. / Santos, C. / Subramanyam, B. / Vergona, R. / Wei, R.G. / Whitlow, M. / Ye, B. / Zhao, Z.S. / Devlin, J.J. / Phillips, G. #1: ジャーナル: Bioorg.Med.Chem.Lett. / 年: 2007 タイトル: The Rational Design of Inhibitors of Nitric Oxide Formation by Inducible Nitric Oxide Synthase 著者: Whitlow, M. / Adler, M. / Davey, D.D. / Huang, Q. / Koovakkat, S. / Pham, E. / Polokoff, M. / Xu, W. / Yuan, S.S. / Phillips, G. #2: ジャーナル: To be Published / 年: 2007 タイトル: 3-[4-(1-Imidazolyl)phenoxy]-1-piperonyl Piperidine Analogs as Potent and Selective Inhibitors of Nitric Oxide Formation 著者: Wei, R.G. / Adler, M. / Davey, D. / Ho, E. / Mohan, R. / Polokoff, M. / Tseng, J.L. / Whitlow, M. / Xu, W. / Yuan, S. / Phillips, G. #3: ジャーナル: Proc.Natl.Acad.Sci.USA / 年: 2000 タイトル: Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry. 著者: McMillan, K. / Adler, M. / Auld, D.S. / Baldwin, J.J. / Blasko, E. / Browne, L.J. / Chelsky, D. / Davey, D. / Dolle, R.E. / Eagen, K.A. / Erickson, S. / Feldman, R.I. / Glaser, C.B. / ...著者: McMillan, K. / Adler, M. / Auld, D.S. / Baldwin, J.J. / Blasko, E. / Browne, L.J. / Chelsky, D. / Davey, D. / Dolle, R.E. / Eagen, K.A. / Erickson, S. / Feldman, R.I. / Glaser, C.B. / Mallari, C. / Morrissey, M.M. / Ohlmeyer, M.H. / Pan, G. / Parkinson, J.F. / Phillips, G.B. / Polokoff, M.A. / Sigal, N.H. / Vergona, R. / Whitlow, M. / Young, T.A. / Devlin, J.J. #4: ジャーナル: Science / 年: 1997 タイトル: The structure of nitric oxide synthase oxygenase domain and inhibitor complexes. 著者: Crane, B.R. / Arvai, A.S. / Gachhui, R. / Wu, C. / Ghosh, D.K. / Getzoff, E.D. / Stuehr, D.J. / Tainer, J.A. #5: ジャーナル: Biochemistry / 年: 1997 タイトル: Characterization of the inducible nitric oxide synthase oxygenase domain identifies a 49 amino acid segment required for subunit dimerization and tetrahydrobiopterin interaction. 著者: Ghosh, D.K. / Wu, C. / Pitters, E. / Moloney, M. / Werner, E.R. / Mayer, B. / Stuehr, D.J. | ||||||
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 | 2orr.cif.gz | 84.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb2orr.ent.gz | 61.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 2orr.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/or/2orr ftp://data.pdbj.org/pub/pdb/validation_reports/or/2orr | 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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1 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 45270.379 Da / 分子数: 1 / 断片: OXYGENASE DOMAIN 114-498 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Nos2, Inosl / プラスミド: PCWORI / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P29477, nitric-oxide synthase (NADPH) | ||
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#2: 化合物 | ChemComp-HEM / | ||
#3: 化合物 | ChemComp-333 / | ||
#4: 化合物 | ChemComp-EDO / #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: 2.42 Å3/Da / 溶媒含有率: 49.1 % |
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結晶化 | 温度: 308 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 4.7 詳細: CRYSTALS OF MURINE DELTA114 INOS WERE PREPARED IN THE PRESENCE OF IMIDAZOLE FOLLOWING THE PROCEDURES OF CRANE ET AL. (REFERENCE 3) AS FOLLOWS: THE 6 UL CRYSTALLIZATION DROPS CONTAINED 20 ...詳細: CRYSTALS OF MURINE DELTA114 INOS WERE PREPARED IN THE PRESENCE OF IMIDAZOLE FOLLOWING THE PROCEDURES OF CRANE ET AL. (REFERENCE 3) AS FOLLOWS: THE 6 UL CRYSTALLIZATION DROPS CONTAINED 20 MG/ML MURINE DELTA114 INOS, 20 MM HEPES PH 7.6, 5 % GLYCEROL, 0.5 MM DTT, 6.8 % PEG-3350, 60 MM NA2SO3, AND 50 MM IMIDAZOLE/ MALATE BUFFER PH 4.7 WERE PLACED OVER A 1 ML RESERVOIR CONTAINING 13.6 % PEG-3350, 120 MM NA2SO3, AND 100 MM IMIDAZOLE/MALATE BUFFER PH 4.7. THESE CRYSTALS WERE SOAKED FOR 25 HOURS IN 5 UM 4-(Benzo[1,3]dioxol-5-yloxy)- 2-(4-imidazol-1-yl-phenoxy)-pyrimidine, 14 % PEG-3350, 1 MM NAN3, 50 MM MES PH 6.5 AND 50 MM NA2SO3. THE, pH 4.70, VAPOR DIFFUSION, HANGING DROP, temperature 308K |
-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: ALS / ビームライン: 5.0.2 / 波長: 1 / 波長: 1 Å | |||||||||
検出器 | タイプ: ADSC QUANTUM 4 / 検出器: CCD / 日付: 1998年8月10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 |
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反射 | 解像度: 1.9→30 Å / Num. obs: 33547 / % possible obs: 95.06 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / 冗長度: 3.21 % / Biso Wilson estimate: 28.3 Å2 / Rsym value: 0.0607 / Net I/σ(I): 16.82 | |||||||||
反射 シェル | 解像度: 1.9→1.96 Å / 冗長度: 2.55 % / Rmerge(I) obs: 0.34 / Mean I/σ(I) obs: 1.5 / % possible all: 74.4 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: フーリエ合成 開始モデル: PDB Entry BX04 解像度: 2→29.14 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 221896.26 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / 交差検証法: THROUGHOUT / σ(F): 2 / σ(I): 0 詳細: ATOMS WITH NO 1.0 SIGMA 2FO-FC DENSITY HAD THEIR OCCUPANCY LOWERED TO 0.5. THE POSITION OF THESE ATOMS SHOULD NOT BE TRUSTED.
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溶媒の処理 | 溶媒モデル: FLAT MODEL / Bsol: 55.6954 Å2 / ksol: 0.333673 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 43.5 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→29.14 Å
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拘束条件 |
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 8
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Xplor file |
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