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Open data
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Basic information
Entry | Database: PDB / ID: 2oc0 | ||||||
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Title | Structure of NS3 complexed with a ketoamide inhibitor SCh491762 | ||||||
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![]() | VIRAL PROTEIN / Hepatitis C Virus / HCV / NS3 protease domain / ketoamide inhibitor | ||||||
Function / homology | ![]() positive regulation of hexokinase activity / : / 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 / hepacivirin / TBC/RABGAPs / host cell mitochondrial membrane / host cell lipid droplet ...positive regulation of hexokinase activity / : / 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 / hepacivirin / TBC/RABGAPs / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated suppression of host TRAF-mediated signal transduction / symbiont-mediated transformation of host cell / 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 / endoplasmic reticulum-Golgi intermediate compartment membrane / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / SH3 domain binding / kinase binding / nucleoside-triphosphate phosphatase / channel activity / viral nucleocapsid / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / entry receptor-mediated virion attachment to host cell / host cell perinuclear region of cytoplasm / RNA helicase activity / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / ribonucleoprotein complex / symbiont-mediated activation of host autophagy / viral translational frameshifting / RNA-directed RNA polymerase / chromatin extrusion motor activity / ATP-dependent H2AZ histone chaperone activity / ATP-dependent H3-H4 histone complex chaperone activity / cohesin loader activity / cysteine-type endopeptidase activity / viral RNA genome replication / DNA clamp loader activity / serine-type endopeptidase activity / RNA-directed RNA polymerase activity / 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 / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Prongay, A.J. / Guo, Z. / Yao, N. / Fischmann, T. / Strickland, C. / Myers Jr., J. / Weber, P.C. / Malcolm, B. / Beyer, B.M. / Ingram, R. ...Prongay, A.J. / Guo, Z. / Yao, N. / Fischmann, T. / Strickland, C. / Myers Jr., 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. / Arasappan, A. / Bennett, F. / Bogen, S.F. / Chen, K. / Jao, E. / Liu, Y. / Love, R.G. / Saksena, A.K. / Venkatraman, S. / Girijavallabhan, V. / Njoroge, F.G. / Madison, V. | ||||||
![]() | ![]() Title: 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- ...Title: 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. Authors: Prongay, A.J. / Guo, Z. / Yao, N. / Pichardo, J. / Fischmann, T. / Strickland, C. / Myers Jr., J. / Weber, P.C. / Beyer, B.M. / Ingram, R. / Hong, Z. / Prosise, W.W. / Ramanathan, L. / ...Authors: Prongay, A.J. / Guo, Z. / Yao, N. / Pichardo, J. / Fischmann, T. / Strickland, C. / Myers Jr., 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: ![]() 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: SAR of P'2 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. / Yao, N. / Marten, B. / Madison, V. / Kemp, S. / Levy, O. / Lim-Wilby, M. / Tamura, S. / Ganguly, A.K. #3: ![]() Title: Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease. Authors: Chen, K.X. / Njoroge, F.G. / Prongay, A. / Pichardo, J. / Madison, V. / Girijavallabhan, V. #4: ![]() 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. #5: ![]() Title: Mutations conferring resistance to SCH6, a novel hepatitis C virus NS3/4A protease inhibitor. Reduced RNA replication fitness and partial rescue by second-site mutations. Authors: Yi, M. / Tong, X. / Skelton, A. / Chase, R. / Chen, T. / Prongay, A. / Bogen, S.L. / Saksena, A.K. / Njoroge, F.G. / Veselenak, R.L. / Pyles, R.B. / Bourne, N. / Malcolm, B.A. / Lemon, S.M. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 92.3 KB | Display | ![]() |
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PDB format | ![]() | 68 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 858.7 KB | Display | ![]() |
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Full document | ![]() | 863.5 KB | Display | |
Data in XML | ![]() | 18.5 KB | Display | |
Data in CIF | ![]() | 26.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 2o8mSC ![]() 2oboC ![]() 2obqC ![]() 2oc1C ![]() 2oc7C ![]() 2oc8C S: Starting model for refinement C: citing same article ( |
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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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Components
-Protein / Protein/peptide , 2 types, 4 molecules ACBD
#1: Protein | Mass: 21233.225 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 2394.039 Da / Num. of mol.: 2 / Mutation: C22S / Source method: obtained synthetically / References: UniProt: Q9QP06, UniProt: P27958*PLUS |
-Non-polymers , 4 types, 214 molecules 






#3: Chemical | |
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#4: Chemical | ChemComp-BME / |
#5: Chemical | ChemComp-HU1 / |
#6: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.86 Å3/Da / Density % sol: 68.15 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 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 ...Details: 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 b-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 b-mercaptoethanol} , VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 95 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.25→50 Å / Num. all: 34251 / Num. obs: 33806 / % possible obs: 98.7 % / Observed criterion σ(I): 2 / Redundancy: 4.2 % / Biso Wilson estimate: 33.9 Å2 / Rsym value: 0.047 / Net I/σ(I): 26.4 |
Reflection shell | Highest resolution: 2.25 Å / Redundancy: 4.2 % / Mean I/σ(I) obs: 2.3 / Rsym value: 0.411 / % possible all: 83.1 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2O8M Resolution: 2.3→8 Å / σ(F): 1
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Refinement step | Cycle: LAST / Resolution: 2.3→8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.4 Å
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