[English] 日本語
Yorodumi- PDB-7ju7: The crystal structure of SARS-CoV-2 Main Protease in complex with... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7ju7 | ||||||
---|---|---|---|---|---|---|---|
Title | The crystal structure of SARS-CoV-2 Main Protease in complex with masitinib | ||||||
Components | 3C-like proteinase | ||||||
Keywords | HYDROLASE / SARS-CoV-2 / COVID-19 / 3CL / main protease / masitinib / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID | ||||||
Function / homology | Function and homology information protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs ...protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / snRNP Assembly / TRAF3-dependent IRF activation pathway / Replication of the SARS-CoV-2 genome / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / : / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / host cell endosome / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / SARS-CoV-2 modulates host translation machinery / omega peptidase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / host cell Golgi apparatus / symbiont-mediated perturbation of host ubiquitin-like protein modification / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / DNA helicase / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / copper ion binding / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Tan, K. / Maltseva, N.I. / Welk, L.F. / Jedrzejczak, R.P. / Joachimiak, A. / Center for Structural Genomics of Infectious Diseases (CSGID) | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Science / Year: 2021 Title: Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Authors: Drayman, N. / DeMarco, J.K. / Jones, K.A. / Azizi, S.A. / Froggatt, H.M. / Tan, K. / Maltseva, N.I. / Chen, S. / Nicolaescu, V. / Dvorkin, S. / Furlong, K. / Kathayat, R.S. / Firpo, M.R. / ...Authors: Drayman, N. / DeMarco, J.K. / Jones, K.A. / Azizi, S.A. / Froggatt, H.M. / Tan, K. / Maltseva, N.I. / Chen, S. / Nicolaescu, V. / Dvorkin, S. / Furlong, K. / Kathayat, R.S. / Firpo, M.R. / Mastrodomenico, V. / Bruce, E.A. / Schmidt, M.M. / Jedrzejczak, R. / Munoz-Alia, M.A. / Schuster, B. / Nair, V. / Han, K.Y. / O'Brien, A. / Tomatsidou, A. / Meyer, B. / Vignuzzi, M. / Missiakas, D. / Botten, J.W. / Brooke, C.B. / Lee, H. / Baker, S.C. / Mounce, B.C. / Heaton, N.S. / Severson, W.E. / Palmer, K.E. / Dickinson, B.C. / Joachimiak, A. / Randall, G. / Tay, S. #1: Journal: Biorxiv / Year: 2020 Title: Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro . Authors: Drayman, N. / Jones, K.A. / Azizi, S.A. / Froggatt, H.M. / Tan, K. / Maltseva, N.I. / Chen, S. / Nicolaescu, V. / Dvorkin, S. / Furlong, K. / Kathayat, R.S. / Firpo, M.R. / Mastrodomenico, V. ...Authors: Drayman, N. / Jones, K.A. / Azizi, S.A. / Froggatt, H.M. / Tan, K. / Maltseva, N.I. / Chen, S. / Nicolaescu, V. / Dvorkin, S. / Furlong, K. / Kathayat, R.S. / Firpo, M.R. / Mastrodomenico, V. / Bruce, E.A. / Schmidt, M.M. / Jedrzejczak, R. / Munoz-Alia, M.A. / Schuster, B. / Nair, V. / Botten, J.W. / Brooke, C.B. / Baker, S.C. / Mounce, B.C. / Heaton, N.S. / Dickinson, B.C. / Jaochimiak, A. / Randall, G. / Tay, S. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7ju7.cif.gz | 167.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7ju7.ent.gz | 108.4 KB | Display | PDB format |
PDBx/mmJSON format | 7ju7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ju/7ju7 ftp://data.pdbj.org/pub/pdb/validation_reports/ju/7ju7 | HTTPS FTP |
---|
-Related structure data
Related structure data | 7l5dC 7jfqS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||||||||
Unit cell |
| |||||||||||||||
Components on special symmetry positions |
|
-Components
#1: Protein | Mass: 33825.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: rep, 1a-1b / Plasmid: pMCSG53 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-Gold(DE3) References: UniProt: P0DTD1, SARS coronavirus main proteinase | ||||
---|---|---|---|---|---|
#2: Chemical | ChemComp-G65 / | ||||
#3: Chemical | ChemComp-DMS / | ||||
#4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.79 Å3/Da / Density % sol: 55.96 % |
---|---|
Crystal grow | Temperature: 296 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 0.2 M NaCl, 0.1 M MES, 20% (w/v) PEG 6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.9791 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Aug 12, 2020 / Details: Mirror |
Radiation | Monochromator: Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9791 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→43.5 Å / Num. obs: 48121 / % possible obs: 98.5 % / Observed criterion σ(I): -3 / Redundancy: 3.5 % / Biso Wilson estimate: 23.98 Å2 / CC1/2: 0.999 / CC star: 1 / Rmerge(I) obs: 0.084 / Rpim(I) all: 0.05 / Rrim(I) all: 0.098 / Χ2: 1.357 / Net I/σ(I): 26.3 |
Reflection shell | Resolution: 1.6→1.63 Å / Redundancy: 2.3 % / Rmerge(I) obs: 0.877 / Mean I/σ(I) obs: 1.1 / Num. unique obs: 2341 / CC1/2: 0.354 / CC star: 0.723 / Rpim(I) all: 0.672 / Rrim(I) all: 1.111 / Χ2: 0.678 / % possible all: 95.4 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7JFQ Resolution: 1.6→43.5 Å / SU ML: 0.1703 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 20.6957 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 33.49 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.6→43.5 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group | Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A
|