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Yorodumi- PDB-6wx4: Crystal structure of the SARS CoV-2 Papain-like protease in compl... -
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Basic information
| Entry | Database: PDB / ID: 6wx4 | |||||||||
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| Title | Crystal structure of the SARS CoV-2 Papain-like protease in complex with peptide inhibitor VIR251 | |||||||||
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Keywords | Hydrolase/Hydrolase Inhibitor / COVID-19 / CORONAVIRUS / SARS / COV-2 / PAPAIN-LIKE PROTEASE / PLpro / deubiquitinating enzyme / ubiquitin / activity-based probe / Hydrolase-Hydrolase Inhibitor complex | |||||||||
| Function / homology | Function and homology informationprotein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity ...protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / snRNP Assembly / Translation of Replicase and Assembly of the Replication Transcription Complex / Replication of the SARS-CoV-2 genome / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / double membrane vesicle viral factory outer membrane / host cell endoplasmic reticulum-Golgi intermediate compartment / SARS coronavirus main proteinase / 5'-3' DNA helicase activity / 3'-5'-RNA exonuclease activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / omega peptidase activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / SARS-CoV-2 modulates host translation machinery / host cell Golgi apparatus / symbiont-mediated suppression of host NF-kappaB cascade / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / regulation of autophagy / viral protein processing / lyase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / copper ion binding / viral translational frameshifting / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / lipid binding / 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 | ![]() synthetic construct (others) | |||||||||
| Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.655 Å | |||||||||
Authors | Lv, Z. / Olsen, S.K. | |||||||||
| Funding support | United States, 1items
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Citation | Journal: Sci Adv / Year: 2020Title: Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti-COVID-19 drug design. Authors: Rut, W. / Lv, Z. / Zmudzinski, M. / Patchett, S. / Nayak, D. / Snipas, S.J. / El Oualid, F. / Huang, T.T. / Bekes, M. / Drag, M. / Olsen, S.K. #1: Journal: Biorxiv / Year: 2020 Title: Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design. Authors: Rut, W. / Lv, Z. / Zmudzinski, M. / Patchett, S. / Nayak, D. / Snipas, S.J. / El Oualid, F. / Huang, T.T. / Bekes, M. / Drag, M. / Olsen, S.K. | |||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6wx4.cif.gz | 150.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb6wx4.ent.gz | 115 KB | Display | PDB format |
| PDBx/mmJSON format | 6wx4.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 6wx4_validation.pdf.gz | 425.6 KB | Display | wwPDB validaton report |
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| Full document | 6wx4_full_validation.pdf.gz | 426 KB | Display | |
| Data in XML | 6wx4_validation.xml.gz | 15.5 KB | Display | |
| Data in CIF | 6wx4_validation.cif.gz | 22.2 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wx/6wx4 ftp://data.pdbj.org/pub/pdb/validation_reports/wx/6wx4 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 6wuuSC 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 on special symmetry positions |
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Components
| #1: Protein | Mass: 37128.145 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: rep, 1a-1b / Plasmid: pET29b / Production host: ![]() References: UniProt: P0DTD1, EC: 3.4.19.121, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases |
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| #2: Protein/peptide | |
| #3: Chemical | ChemComp-ZN / |
| #4: Water | ChemComp-HOH / |
| Compound details | Peptide covalently linked to active site Cys |
| Has ligand of interest | Y |
-Experimental details
-Experiment
| Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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Sample preparation
| Crystal | Density Matthews: 2.56 Å3/Da / Density % sol: 51.88 % |
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| Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop Details: 0.8 M Potassium sodium tartrate tetrahydrate, 0.1 M Tris HCl pH 8.5 and 0.5% w/v Polyethylene glycol monomethyl ether 5,000 |
-Data collection
| Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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| Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 1 Å | ||||||||||||||||||||||||||||||
| Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: May 8, 2020 | ||||||||||||||||||||||||||||||
| Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
| Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
| Reflection | Resolution: 1.65→90.73 Å / Num. obs: 46470 / % possible obs: 99.5 % / Redundancy: 13.2 % / Biso Wilson estimate: 28.43 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.094 / Rpim(I) all: 0.027 / Rrim(I) all: 0.098 / Net I/σ(I): 15.5 / Num. measured all: 611490 / Scaling rejects: 50 | ||||||||||||||||||||||||||||||
| Reflection shell | Diffraction-ID: 1
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-Phasing
| Phasing | Method: molecular replacement |
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Processing
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| Refinement | Method to determine structure: MOLECULAR REPLACEMENTStarting model: 6WUU Resolution: 1.655→90.729 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 18.05 / Stereochemistry target values: ML
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| Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Displacement parameters | Biso max: 136.3 Å2 / Biso mean: 37.6917 Å2 / Biso min: 19.13 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Refinement step | Cycle: final / Resolution: 1.655→90.729 Å
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| Refine LS restraints |
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| LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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| Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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| Refinement TLS group |
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X-RAY DIFFRACTION
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