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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 2oc8 | |||||||||
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タイトル | Structure of Hepatitis C Viral NS3 protease domain complexed with NS4A peptide and ketoamide SCH503034 | |||||||||
![]() | (Hepatitis C virus) x 2 | |||||||||
![]() | VIRAL PROTEIN / Hepatitis C Virus / HCV / NS3 protease domain / ketoamide inhibitor | |||||||||
機能・相同性 | ![]() positive regulation of hexokinase activity / modulation by virus of host cellular process / translocation of peptides or proteins into host cell cytoplasm / Toll-like receptor 2 binding / viral capsid assembly / adhesion receptor-mediated virion attachment to host cell / TBC/RABGAPs / hepacivirin / host cell mitochondrial membrane / host cell lipid droplet ...positive regulation of hexokinase activity / modulation by virus of host cellular process / translocation of peptides or proteins into host cell cytoplasm / Toll-like receptor 2 binding / viral capsid assembly / adhesion receptor-mediated virion attachment to host cell / TBC/RABGAPs / hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated suppression of host TRAF-mediated signal transduction / transformation of host cell by virus / positive regulation of cytokinesis / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / negative regulation of protein secretion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / endoplasmic reticulum-Golgi intermediate compartment membrane / lipid droplet / kinase binding / SH3 domain binding / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / viral nucleocapsid / clathrin-dependent endocytosis of virus by host cell / entry receptor-mediated virion attachment to host cell / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / ribonucleoprotein complex / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
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手法 | ![]() ![]() ![]() | |||||||||
![]() | Prongay, A.J. / Guo, Z. / Yao, N. / Fischmann, T. / Strickland, C. / Myers, J. / Weber, P.C. / Malcolm, B. / Beyer, B.M. / Ingram, R. ...Prongay, A.J. / Guo, Z. / Yao, N. / Fischmann, T. / Strickland, C. / Myers, J. / Weber, P.C. / Malcolm, B. / Beyer, B.M. / Ingram, R. / Pichardo, J. / Hong, Z. / Prosise, W.W. / Ramanathan, L. / Taremi, S.S. / Yarosh-Tomaine, T. / Zhang, R. / Senior, M. / Yang, R.S. / Arasappan, A. / Bennett, F. / Bogen, S.L. / Chen, K. / Jao, E. / Liu, Y.T. / Lovey, R.G. / Saksena, A.K. / Venkatraman, S. / Girijavallabhan, V. / Njoroge, F.G. / Madison, V. | |||||||||
![]() | ![]() タイトル: Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- ...タイトル: Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure-based optimization. 著者: Prongay, A.J. / Guo, Z. / Yao, N. / Pichardo, J. / Fischmann, T. / Strickland, C. / Myers, J. / Weber, P.C. / Beyer, B.M. / Ingram, R. / Hong, Z. / Prosise, W.W. / Ramanathan, L. / Taremi, S. ...著者: Prongay, A.J. / Guo, Z. / Yao, N. / Pichardo, J. / Fischmann, T. / Strickland, C. / Myers, J. / Weber, P.C. / Beyer, B.M. / Ingram, R. / Hong, Z. / Prosise, W.W. / Ramanathan, L. / Taremi, S.S. / Yarosh-Tomaine, T. / Zhang, R. / Senior, M. / Yang, R.S. / Malcolm, B. / Arasappan, A. / Bennett, F. / Bogen, S.L. / Chen, K. / Jao, E. / Liu, Y.T. / Lovey, R.G. / Saksena, A.K. / Venkatraman, S. / Girijavallabhan, V. / Njoroge, F.G. / Madison, V. #1: ![]() タイトル: Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. 著者: Kim, J.L. / Morgenstern, K.A. / Lin, C. / Fox, T. / Dwyer, M.D. / Landro, J.A. / Chambers, S.P. / Markland, W. / Lepre, C.A. / O'Malley, E.T. / Harbeson, S.L. / Rice, C.M. / Murcko, M.A. / ...著者: Kim, J.L. / Morgenstern, K.A. / Lin, C. / Fox, T. / Dwyer, M.D. / Landro, J.A. / Chambers, S.P. / Markland, W. / Lepre, C.A. / O'Malley, E.T. / Harbeson, S.L. / Rice, C.M. / Murcko, M.A. / Caron, P.R. / Thomson, J.A. #2: ![]() タイトル: Hepatitis C virus NS3-4A serine protease inhibitors: SAR of P'2 moiety with improved potency. 著者: Arasappan, A. / Njoroge, F.G. / Chan, T.Y. / Bennett, F. / Bogen, S.L. / Chen, K. / Gu, H. / Hong, L. / Jao, E. / Liu, Y.T. / Lovey, R.G. / Parekh, T. / Pike, R.E. / Pinto, P. / Santhanam, B. ...著者: Arasappan, A. / Njoroge, F.G. / Chan, T.Y. / Bennett, F. / Bogen, S.L. / Chen, K. / Gu, H. / Hong, L. / Jao, E. / Liu, Y.T. / Lovey, R.G. / Parekh, T. / Pike, R.E. / Pinto, P. / Santhanam, B. / Venkatraman, S. / Vaccaro, H. / Wang, H. / Yang, X. / Zhu, Z. / Mckittrick, B. / Saksena, A.K. / Girijavallabhan, V. / Pichardo, J. / Butkiewicz, N. / Ingram, R. / Malcolm, B. / Prongay, A. / Yao, N. / Marten, B. / Madison, V. / Kemp, S. / Levy, O. / Lim-Wilby, M. / Tamura, S. / Ganguly, A.K. #3: ![]() タイトル: Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease. 著者: Chen, K.X. / Njoroge, F.G. / Prongay, A. / Pichardo, J. / Madison, V. / Girijavallabhan, V. #4: ![]() タイトル: Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency. 著者: Bogen, S. / Saksena, A.K. / Arasappan, A. / Gu, H. / Njoroge, F.G. / Girijavallabhan, V. / Pichardo, J. / Butkiewicz, N. / Prongay, A. / Madison, V. #5: ![]() タイトル: Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity. 著者: Bogen, S.L. / Ruan, S. / Liu, R. / Agrawal, S. / Pichardo, J. / Prongay, A. / Baroudy, B. / Saksena, A.K. / Girijavallabhan, V. / Njoroge, F.G. | |||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 91.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 67.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 843.7 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 854.2 KB | 表示 | |
XML形式データ | ![]() | 18.6 KB | 表示 | |
CIF形式データ | ![]() | 25.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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単位格子 |
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要素
-タンパク質 / タンパク質・ペプチド , 2種, 4分子 ACBD
#1: タンパク質 | 分子量: 21233.225 Da / 分子数: 2 断片: NS3 protease domain (N-terminal T7 epitope -NS3 residues 1-181-C-terminal His Tag) with bound Zn, Chain A and C 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質・ペプチド | 分子量: 2394.039 Da / 分子数: 2 断片: NS4a peptide (KK-NS4a residues 21-39-KK), Chain B and D Mutation: C22S / 由来タイプ: 合成 / 参照: UniProt: Q9QP06, UniProt: P27958*PLUS |
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-非ポリマー , 4種, 142分子 ![](data/chem/img/ZN.gif)
![](data/chem/img/BME.gif)
![](data/chem/img/U5G.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/BME.gif)
![](data/chem/img/U5G.gif)
![](data/chem/img/HOH.gif)
#3: 化合物 | #4: 化合物 | ChemComp-BME / | #5: 化合物 | ChemComp-U5G / | #6: 水 | ChemComp-HOH / | |
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-実験情報
-実験
実験 | 手法: ![]() |
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試料調製
結晶 | マシュー密度: 3.82 Å3/Da / 溶媒含有率: 67.83 % |
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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: 5.6 詳細: The protein (NS3 complexed with KK-NS4a(21-39)-KK peptide) was at 12-15 mg/ml in 15 mM MES, pH 6.5, 1 M NaCl, 20 mM b-mercaptoethanol. Hanging Drops were formed by mixing 4:l protein solution ...詳細: The protein (NS3 complexed with KK-NS4a(21-39)-KK peptide) was at 12-15 mg/ml in 15 mM MES, pH 6.5, 1 M NaCl, 20 mM b-mercaptoethanol. Hanging Drops were formed by mixing 4:l protein solution with 4:l {0.75-1.0 M NaCl, 0.1M Na/K phosphate, 0.1 M Mes, pH 5.8-6.1, 20 mM 2-mercaptoethanol} The drop was equilibrated the drops over 1 ml {(1.25-1.50 M) NaCl - 0.1M Na/K phosphate 0.1 M Mes, pH 5.6-5.8, 20 mM 2-mercaptoethanol} , VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-データ収集
回折 | 平均測定温度: 95 K |
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放射光源 | 由来: ![]() ![]() ![]() |
検出器 | タイプ: ADSC QUANTUM 210 / 検出器: CCD |
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 Å / 相対比: 1 |
反射 | 解像度: 2.65→50 Å / Num. all: 20923 / Num. obs: 20317 / % possible obs: 97.1 % / Observed criterion σ(I): 1 / 冗長度: 5.3 % / Biso Wilson estimate: 39.5 Å2 / Rsym value: 0.041 / Net I/σ(I): 31.6 |
反射 シェル | 最高解像度: 2.65 Å / 冗長度: 5.3 % / Mean I/σ(I) obs: 3.5 / Rsym value: 0.257 / % possible all: 70 |
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解析
ソフトウェア |
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精密化 | 構造決定の手法: ![]() 開始モデル: 2O8M 解像度: 2.66→8 Å / Isotropic thermal model: ISOTROPIC / 交差検証法: THROUGHOUT / σ(F): 1 / 立体化学のターゲット値: Engh & Huber
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精密化ステップ | サイクル: LAST / 解像度: 2.66→8 Å
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LS精密化 シェル | 解像度: 2.66→2.78 Å
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