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- PDB-2f9u: HCV NS3 protease domain with NS4a peptide and a ketoamide inhibit... -
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Open data
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Basic information
Entry | Database: PDB / ID: 2f9u | ||||||
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Title | HCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with a P2 norborane | ||||||
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![]() | VIRAL PROTEIN / HCV / Hepatitis C protease / NS3 protease / ketoamide inhibitor | ||||||
Function / homology | ![]() self proteolysis / transformation of host cell by virus / host cell membrane / serine-type peptidase activity / virion component / symbiont entry into host cell / virion attachment to host cell / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Venkatraman, S. / Njoroge, F.G. / Wu, W. / Girijavallabhan, V. / Prongay, A.J. / Butkiewicz, N. / Pichardo, J. | ||||||
![]() | ![]() Title: Novel Inhibitors of Hepatitis C NS3-NS4A Serine Protease Derived from 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid. Authors: Venkatraman, S. / Njoroge, F.G. / Wu, W. / Girijavallabhan, V. / Prongay, A.J. / Butkiewicz, N. / Pichardo, J. #1: ![]() 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: ![]() Title: Hepatitis C virus NS3-4A serine protease inhibitors: Use of a P2-P1 cyclopropyl alanine combination to improve potency. Authors: Bogen, S. / Saksena, A.K. / Arasappan, A. / Gu, N. / Njoroge, F.G. / Girijavallabhan, V. / Pichardo, J. / Butkiewicz, N. / Prongay, A. / Madison, A. #3: Journal: J.Med.Chem. / Year: 2005 Title: Design and Synthesis of Depeptidized Macrocyclic Inhibitors of Hepatitis C NS3-4A Protease Using Structure-Based Drug Design Authors: Venkatraman, S. / Njoroge, F.G. / Girijavallabhan, V.M. / Madison, V.S. / Yao, N.H. / Prongay, A.J. / Butkiewicz, N. / Pichardo, J. #4: Journal: Angew.Chem.Int.Ed.Engl. / Year: 2005 Title: Proline-Based Macrocyclic Inhibitors of the Hepatitis C Virus: Stereoselective Synthesis and Biological Activity. Authors: Chen, K.X. / Njoroge, F.G. / Vibulbhan, B. / Prongay, A. / Pichardo, J. / Madison, V. / Buevich, A. / Chan, T.M. #5: Journal: Bioorg.Med.Chem.Lett. / Year: 2004 Title: Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as Hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity and X-ray crystal structure of an enzyme inhibitor complex Authors: Arasappan, A. / Njoroge, F.G. / Parekh, T.N. / Yang, X. / Pichardo, J. / Butkiewicz, N. / Prongay, A. / Yao, N. / Girijavallabhan, V. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 89.9 KB | Display | ![]() |
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PDB format | ![]() | 67.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 802.8 KB | Display | ![]() |
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Full document | ![]() | 812.6 KB | Display | |
Data in XML | ![]() | 18.1 KB | Display | |
Data in CIF | ![]() | 24.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Details | The NS3 protease domain, residues 1-181 of NS3, exists in a complex with an NS4a peptide and an inhibitor. There is a dimer of the NS3 domain-NS4a peptide complex, but only one monomer (Chains A and B) have the inhibitor bound to the active site. This dimer is the component of the asymmetric unit. In vivo, the protease domain is part of a multi enzyme protein (having both protease and helicase activities). The NS3 protease domain with the NS4A peptide is known to be catalytically active in the absence of the helicase domain, although it is not known whether it is active as a monomer or dimer. |
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Components
#1: Protein | Mass: 21102.027 Da / Num. of mol.: 2 / Fragment: protease domain (Residues : 1-181) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: NS3 protease domain ( residues 1027-1207 of the polyprotein). Plasmid: NS3(181)His6/pET22b / Production host: ![]() ![]() #2: Protein/peptide | Mass: 2394.039 Da / Num. of mol.: 2 / Fragment: Residues: 21-39 / Source method: obtained synthetically Details: Solid-phase peptide synthesis of the NS4a residues 21-39 peptide with N-terminal KK and C-terminal KK extensions. References: GenBank: 51039195 #3: Chemical | #4: Chemical | ChemComp-5NH / | #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.91 Å3/Da / Density % sol: 68.54 % |
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Crystal grow | Temperature: 285 K / pH: 5.7 Details: 12-15 mG/mL Protein in 15 mM MES, pH 6.5 - 1.0 M NaCl equivolume mixture with (0.85-1.05M) NaCl- 0.1M MES-0.1 M Na/KPO4, pH5.5-5.8 - 5mM BME, equilibrated with 1.35-1.55M NaCl-0.1M MES-0.1M ...Details: 12-15 mG/mL Protein in 15 mM MES, pH 6.5 - 1.0 M NaCl equivolume mixture with (0.85-1.05M) NaCl- 0.1M MES-0.1 M Na/KPO4, pH5.5-5.8 - 5mM BME, equilibrated with 1.35-1.55M NaCl-0.1M MES-0.1M Na/KPO4, pH 5.6-5.8 - 5 mM BME, VAPOR DIFFUSION, HANGING DROP, temperature 285K, pH 5.70 |
-Data collection
Diffraction | Mean temperature: 95 K |
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Diffraction source | Source: ![]() |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Oct 25, 2005 / Details: OSMIC GREEN |
Radiation | Monochromator: OSMIC GREEN / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→50 Å / Num. obs: 20873 / % possible obs: 92.7 % / Observed criterion σ(I): 1.3 / Redundancy: 4.6 % / Biso Wilson estimate: 35.89 Å2 / Rmerge(I) obs: 0.075 / Net I/σ(I): 18.4 |
Reflection shell | Resolution: 2.6→2.66 Å / Redundancy: 1.6 % / Rmerge(I) obs: 0.49 / Mean I/σ(I) obs: 1.3 / % possible all: 42 |
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Processing
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Refinement | Method to determine structure: ![]()
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Refinement step | Cycle: LAST / Resolution: 2.6→8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.6→2.71 Å / Total num. of bins used: 8
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