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Yorodumi- PDB-3bsc: Crystal Structure of HCV NS5B Polymerase with a Novel Pyridazinon... -
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-Basic information
Entry | Database: PDB / ID: 3bsc | ||||||
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Title | Crystal Structure of HCV NS5B Polymerase with a Novel Pyridazinone Inhibitor | ||||||
Components | RNA-directed RNA polymerase | ||||||
Keywords | TRANSFERASE / PROTEIN-LIGAND COMPLEX / RNA replication / RNA-binding / RNA-directed RNA polymerase / Transcription / Transcription regulation / Transmembrane / Viral nucleoprotein | ||||||
Function / homology | Function and homology information hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated suppression of host TRAF-mediated signal transduction / transformation of host cell by virus / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / 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 / SH3 domain binding / nucleoside-triphosphate phosphatase ...hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated suppression of host TRAF-mediated signal transduction / transformation of host cell by virus / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / 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 / SH3 domain binding / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / viral nucleocapsid / clathrin-dependent endocytosis of virus by 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 / 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 / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane Similarity search - Function | ||||||
Biological species | Hepatitis C virus | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.65 Å | ||||||
Authors | Zhao, Q. / Showalter, R.E. / Han, Q. / Kissinger, C.R. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2008 Title: Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1: exploration of 7'-substitution of benzothiadiazine. Authors: Zhou, Y. / Webber, S.E. / Murphy, D.E. / Li, L.S. / Dragovich, P.S. / Tran, C.V. / Sun, Z. / Ruebsam, F. / Shah, A.M. / Tsan, M. / Showalter, R.E. / Patel, R. / Li, B. / Zhao, Q. / Han, Q. / ...Authors: Zhou, Y. / Webber, S.E. / Murphy, D.E. / Li, L.S. / Dragovich, P.S. / Tran, C.V. / Sun, Z. / Ruebsam, F. / Shah, A.M. / Tsan, M. / Showalter, R.E. / Patel, R. / Li, B. / Zhao, Q. / Han, Q. / Hermann, T. / Kissinger, C.R. / Lebrun, L. / Sergeeva, M.V. / Kirkovsky, L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3bsc.cif.gz | 226.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3bsc.ent.gz | 183.2 KB | Display | PDB format |
PDBx/mmJSON format | 3bsc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3bsc_validation.pdf.gz | 883.3 KB | Display | wwPDB validaton report |
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Full document | 3bsc_full_validation.pdf.gz | 894.2 KB | Display | |
Data in XML | 3bsc_validation.xml.gz | 41.5 KB | Display | |
Data in CIF | 3bsc_validation.cif.gz | 57.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bs/3bsc ftp://data.pdbj.org/pub/pdb/validation_reports/bs/3bsc | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 64345.738 Da / Num. of mol.: 2 Fragment: HCV NS5B catalytic domain, residues 2420-2989 of polyprotein Mutation: Q544R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Hepatitis C virus (isolate BK) / Strain: Genotype 1b BK / Plasmid: PET21A / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)STAR / References: UniProt: P26663, RNA-directed RNA polymerase #2: Chemical | #3: 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 | Density Matthews: 2.25 Å3/Da / Density % sol: 45.29 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.6 Details: 20% PEG 4K, 50 mM Ammonium Sulfate, 100 mM Sodium Acetate pH 4.7, 5 mM DTT. Transferred to pH 7.6 for soaking., VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Details: MIRRORS |
Radiation | Monochromator: OSMIC MIRRORS / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.65→29.8 Å / Num. all: 34268 / Num. obs: 34268 / % possible obs: 99.7 % / Observed criterion σ(F): 0 / Redundancy: 5.4 % / Biso Wilson estimate: 45.1 Å2 / Rmerge(I) obs: 0.158 / Net I/σ(I): 9.4 |
Reflection shell | Resolution: 2.65→2.74 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.621 / Mean I/σ(I) obs: 2.2 / Num. unique all: 3358 / % possible all: 99.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: HCV POLYMERASE Resolution: 2.65→29.8 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.891 / SU B: 12.703 / SU ML: 0.272 / Isotropic thermal model: ISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.392 / Stereochemistry target values: Engh & Huber
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 43.304 Å2
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Refinement step | Cycle: LAST / Resolution: 2.65→29.8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.65→2.718 Å / Total num. of bins used: 20
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