[English] 日本語
![](img/lk-miru.gif)
- PDB-3eyd: Structure of HCV NS3-4A Protease with an Inhibitor Derived from a... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 3eyd | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of HCV NS3-4A Protease with an Inhibitor Derived from a Boronic Acid | ||||||
![]() |
| ||||||
![]() | VIRAL PROTEIN / Hepatitis C Virus / NS3 Protease Domain / serine protease / boronic acid inhibitor / Envelope protein / Helicase / Hydrolase / Nucleotide-binding / RNA replication / Transmembrane | ||||||
Function / homology | ![]() 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 / ribonucleoside triphosphate phosphatase activity / lipid droplet ...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 / ribonucleoside triphosphate phosphatase activity / lipid droplet / 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 / 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 / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Venkatraman, S. / Wu, W. / Prongay, A.J. / Girijavallabhan, V. / Njoroge, F.G. | ||||||
![]() | ![]() Title: Potent inhibitors of HCV-NS3 protease derived from boronic acids. Authors: Venkatraman, S. / Wu, W. / Prongay, A. / Girijavallabhan, V. / George Njoroge, F. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 91.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 68.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 801 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 806 KB | Display | |
Data in XML | ![]() | 19.2 KB | Display | |
Data in CIF | ![]() | 27.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Similar structure data |
---|
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 | ![]()
| ||||||||
2 | ![]()
| ||||||||
3 |
| ||||||||
Unit cell |
| ||||||||
Details | The asymmetric unit contains a dimer of the NS3-NS4a complex. This is only the protease domain of NS3 and a peptide of NS4a. This dimeric structure is the result of the soultion structure of the domain. The full length NS3 contains a 3-domain helicase as well and would not have the same dimeric interfaces. |
-
Components
#1: Protein | Mass: 21233.225 Da / Num. of mol.: 2 / Fragment: Protease domain, UNP residues 1027-1207 Source method: isolated from a genetically manipulated source Details: T7 epitope (MASMTGGQQMG) followed by HCV NS3 residues 1-181 the SGHHHHHH Source: (gene. exp.) ![]() ![]() ![]() #2: Protein/peptide | Mass: 2394.039 Da / Num. of mol.: 2 / Fragment: UNP residues 1678-1696 / Mutation: C22S / Source method: obtained synthetically Details: Peptides were synthesized using Fmoc solid-phase chemistry on an ABI 431 synthesizer (Foster City, CA). Preloaded 2-chlorotrityl chloride resin or Wang resin was used for the solid phase ...Details: Peptides were synthesized using Fmoc solid-phase chemistry on an ABI 431 synthesizer (Foster City, CA). Preloaded 2-chlorotrityl chloride resin or Wang resin was used for the solid phase assembly of NS4A activator peptide. The sequence of the peptide was Lys-Lys-Gly-Ser-Val-Val-Ile-Val-Gly-Arg-Ile-Ile-Leu-Ser-Gly-Arg-Pro-Ala-Ile-Val-Pro-Lys-Lys-OH. Trifunctional residue sidechain protecting groups included tert-butyl for Ser, tert-butoxycarbonyl for Lys, and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl for Arg. Cleavage and sidechain deprotection was accomplished using 92.5% trifluoroacetic acid, with 2.5% each of water, ethanedithiol and triisopropylsilane for 2 hours. The peptide was purified by reversed phase HPLC. The peptide molecular weight was confirmed by electrospray ionization mass spectrometry. References: UniProt: Q9ELS8, UniProt: P26664*PLUS #3: Chemical | #4: Chemical | ChemComp-BE8 / [( | #5: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 3.89 Å3/Da / Density % sol: 68.37 % |
---|---|
Crystal grow | Method: vapor diffusion, hanging drop / pH: 5.6 Details: Crystallization was performed by the vapor diffusion method using hanging drops (4 L protein solution mixed with 4 L (0.75 - 1.00) M NaCl - 0.1 M MES - 0.1 M Na/K PO4, pH 5.6 - 6.2) ...Details: Crystallization was performed by the vapor diffusion method using hanging drops (4 L protein solution mixed with 4 L (0.75 - 1.00) M NaCl - 0.1 M MES - 0.1 M Na/K PO4, pH 5.6 - 6.2) suspended over 1 mL reservoir solutions of (1.25 - 1.50) M NaCl - 0.1 M MES - 0.1 M Na/K PO4 - 5 mM -mercaptoethanol, pH 5.6-6.2. The trays were set at 4oC for 5-7 days to control nucleation, followed by incubation for 3 weeks at 12oC to maximize crystal growth., VAPOR DIFFUSION, HANGING DROP, temperature 277, then 285K Temp details: 277, then 285 |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Apr 7, 2004 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.15→50 Å / Num. all: 39911 / Num. obs: 28576 / % possible obs: 71.6 % / Observed criterion σ(I): 1 / Redundancy: 2.8 % / Rmerge(I) obs: 0.075 / Net I/σ(I): 13.5 |
Reflection shell | Resolution: 2.15→2.2 Å / Rmerge(I) obs: 0.288 / Mean I/σ(I) obs: 2 / Num. unique all: 2631 / % possible all: 20.6 |
-
Processing
Software |
| |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: HCV NS3(1-181)S139A - NS4a pdb2o8m.ent Resolution: 2.3→8 Å / Isotropic thermal model: anoistropic / Cross valid method: THROUGHOUT / σ(F): 1
| |||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3→8 Å
| |||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||
LS refinement shell | Resolution: 2.3→2.4 Å
|