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Yorodumi- PDB-2a4r: HCV NS3 Protease Domain with a Ketoamide Inhibitor Covalently bound. -
+Open data
-Basic information
Entry | Database: PDB / ID: 2a4r | ||||||
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Title | HCV NS3 Protease Domain with a Ketoamide Inhibitor Covalently bound. | ||||||
Components |
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Keywords | VIRAL PROTEIN | ||||||
Function / homology | Function and homology information 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 / self proteolysis / viral capsid assembly / adhesion receptor-mediated virion attachment to host cell / TBC/RABGAPs / hepacivirin / host cell mitochondrial membrane ...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 / self proteolysis / 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 / host cell membrane / negative regulation of protein secretion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / viral process / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / serine-type peptidase activity / endoplasmic reticulum-Golgi intermediate compartment membrane / kinase binding / SH3 domain binding / virion component / 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 / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / 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 / symbiont entry into host cell / induction by virus of host autophagy / serine-type endopeptidase activity / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / apoptotic process / 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 / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | Hepatitis C virus | ||||||
Method | X-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 2.4 Å | ||||||
Authors | Bogen, S. / Saksena, A.K. / Arasappan, A. / Gu, H. / Njoroge, F.G. / Girijavallabhan, V. / Pichardo, J. / Butkiewicz, N. / Prongay, A. / Madison, V. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2005 Title: Hepatitis C Virus NS3-4A serine protease inhibitors: Use of a P2-P1 cyclopropyl alanine combination for improved potency. Authors: Bogen, S. / Saksena, A.K. / Arasappan, A. / Gu, H. / Njoroge, F.G. / Girijavallabhan, V. / Pichardo, J. / Butkiewicz, N. / Prongay, A. / Madison, V. #1: Journal: Cell(Cambridge,Mass.) / Year: 1996 Title: Crystal Structure of the Hepatitis C Virus NS3 Protease Domain Complexed with a Synthetic NS4a Cofactor Peptide Authors: 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. / ...Authors: 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: Journal: Bioorg.Med.Chem.Lett. / Year: 2005 Title: Hepatitis C virus NS3-4A serine protease inhibitors. SAR of P2' moiety with improved potency. Authors: 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. ...Authors: 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.J. / Yao, N. / Marten, B. / Madison, V. / Kemp, S. / Levy, O. / Lim-Wilby, M. / Tamura, S. / Ganguly, A.K. #3: Journal: Cell(Cambridge,Mass.) / Year: 1996 Title: The Crystal Structure of Hepatitis C Virus NS3 proteinase Reveals a Trypsin-like fold and a Structural Zinc Binding Site. Authors: Love, R.A. / Parge, H.E. / Wickersham, J.A. / Hostomsky, Z. / Habuka, N. / Moomaw, E.W. / Adachi, T. / Hostomska, Z. #4: Journal: Protein Sci. / Year: 1998 Title: Complex of NS3 protease and NS4a peptide of BK strain hepatitis C virus: A 2.2A resolution structure in a hexagonal crystal form. Authors: Yan, Y. / Li, Y. / Munshi, S. / Sardana, V. / Cole, J.L. / Sardana, M. / Steinkuehler, C. / Tomei, L. / De Francesco, R. / Kuo, L.C. / Chen, Z. #5: Journal: J.Biol.Chem. / Year: 2000 Title: Inhibition of the Hepatitis C Virus NS3/4A Protease. The Crystal Structures of Two protease-inhibitor complexes. Authors: DiMarco, S. / Rizzi, M. / Volpari, C. / Walsh, M.A. / Narjes, F. / Colarusso, S. / De Francesco, R. / Matassa, V.G. / Sollazzo, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2a4r.cif.gz | 89.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2a4r.ent.gz | 66.7 KB | Display | PDB format |
PDBx/mmJSON format | 2a4r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2a4r_validation.pdf.gz | 765.8 KB | Display | wwPDB validaton report |
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Full document | 2a4r_full_validation.pdf.gz | 772.9 KB | Display | |
Data in XML | 2a4r_validation.xml.gz | 18.2 KB | Display | |
Data in CIF | 2a4r_validation.cif.gz | 25.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a4/2a4r ftp://data.pdbj.org/pub/pdb/validation_reports/a4/2a4r | HTTPS FTP |
-Related structure data
Related structure data | |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 21233.225 Da / Num. of mol.: 2 / Fragment: protease domain, residues 1-181 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Hepatitis C virus / Genus: Hepacivirus / Production host: Escherichia coli (E. coli) / References: UniProt: Q91RS4, UniProt: P27958*PLUS #2: Protein/peptide | Mass: 2394.039 Da / Num. of mol.: 2 / Fragment: residues 21-39 / Source method: obtained synthetically Details: THE PEPTIDE WAS CHEMICALLY SYNTHESIZED. THE SEQUENCE OF THE PROTEIN IS NATURALLY FOUND IN HEPATITIS C VIRUS TYPE 1B. References: UniProt: O39914, UniProt: P27958*PLUS #3: Chemical | #4: Chemical | ChemComp-BNH / [( | #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal |
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Crystal grow |
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-Data collection
Diffraction | Mean temperature: 95 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Apr 8, 1999 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→100 Å / Num. all: 28197 / Num. obs: 28197 / % possible obs: 99.2 % / Observed criterion σ(I): 2.4 / Redundancy: 3.5 % / Rmerge(I) obs: 0.047 / Net I/σ(I): 23.3 |
Reflection shell | Resolution: 2.4→2.49 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.489 / Mean I/σ(I) obs: 24 / Num. unique all: 2777 / % possible all: 98.8 |
-Processing
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Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 2.4→8 Å / Isotropic thermal model: ISOTROPIC / Cross valid method: THROUGHOUT / σ(I): 2.36 / Stereochemistry target values: Engh & Huber
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Refinement step | Cycle: LAST / Resolution: 2.4→8 Å
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Refine LS restraints |
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LS refinement shell |
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