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Yorodumi- PDB-7aeh: SARS-CoV-2 main protease in a covalent complex with a pyridine de... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7aeh | |||||||||
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Title | SARS-CoV-2 main protease in a covalent complex with a pyridine derivative of ABT-957, compound 1 | |||||||||
Components | 3C-like proteinase nsp5 | |||||||||
Keywords | HYDROLASE / covid-19 / inhibitor / protease | |||||||||
Function / homology | Function and homology information protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / 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 / Lyases; Phosphorus-oxygen lyases / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / 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 / TRAF3-dependent IRF activation pathway / Replication of the SARS-CoV-2 genome / snRNP Assembly / double membrane vesicle viral factory outer membrane / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / 5'-3' DNA helicase activity / SARS coronavirus main proteinase / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / host cell endosome / 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 / omega peptidase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / host cell Golgi apparatus / methyltransferase cap1 / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / viral protein processing / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / copper ion binding / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent 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 | Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.3 Å | |||||||||
Authors | Owen, C.D. / Redhead, M.A. / Lukacik, P. / Strain-Damerell, C. / Fearon, D. / Brewitz, L. / Collette, A. / Robinson, C. / Collins, P. / Radoux, C. ...Owen, C.D. / Redhead, M.A. / Lukacik, P. / Strain-Damerell, C. / Fearon, D. / Brewitz, L. / Collette, A. / Robinson, C. / Collins, P. / Radoux, C. / Navratilova, I. / Douangamath, A. / von Delft, F. / Malla, T.R. / Nugen, T. / Hull, H. / Tumber, A. / Schofield, C.J. / Hallet, D. / Stuart, D.I. / Hopkins, A.L. / Walsh, M.A. | |||||||||
Citation | Journal: Sci Rep / Year: 2021 Title: Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19. Authors: Redhead, M.A. / Owen, C.D. / Brewitz, L. / Collette, A.H. / Lukacik, P. / Strain-Damerell, C. / Robinson, S.W. / Collins, P.M. / Schafer, P. / Swindells, M. / Radoux, C.J. / Hopkins, I.N. / ...Authors: Redhead, M.A. / Owen, C.D. / Brewitz, L. / Collette, A.H. / Lukacik, P. / Strain-Damerell, C. / Robinson, S.W. / Collins, P.M. / Schafer, P. / Swindells, M. / Radoux, C.J. / Hopkins, I.N. / Fearon, D. / Douangamath, A. / von Delft, F. / Malla, T.R. / Vangeel, L. / Vercruysse, T. / Thibaut, J. / Leyssen, P. / Nguyen, T.T. / Hull, M. / Tumber, A. / Hallett, D.J. / Schofield, C.J. / Stuart, D.I. / Hopkins, A.L. / Walsh, M.A. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7aeh.cif.gz | 154.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7aeh.ent.gz | 119.5 KB | Display | PDB format |
PDBx/mmJSON format | 7aeh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7aeh_validation.pdf.gz | 894.6 KB | Display | wwPDB validaton report |
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Full document | 7aeh_full_validation.pdf.gz | 895.9 KB | Display | |
Data in XML | 7aeh_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | 7aeh_validation.cif.gz | 25 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ae/7aeh ftp://data.pdbj.org/pub/pdb/validation_reports/ae/7aeh | HTTPS FTP |
-Related structure data
Related structure data | 7aegC 5r8tS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 33697.418 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 / Production host: Escherichia coli (E. coli) References: UniProt: P0DTD1, SARS coronavirus main proteinase | ||||||
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#2: Chemical | ChemComp-DMS / #3: Chemical | ChemComp-R8H / ( | #4: Water | ChemComp-HOH / | 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: 1.96 Å3/Da / Density % sol: 37.16 % / Description: square plates |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: Mpro was thawed and diluted to 6 mg/ml using 20 mM Hepes pH 7.5, 50 mM NaCl. The ligand of interest was dissolved in DMSO to 10 mM and then diluted into the protein solution to a final ...Details: Mpro was thawed and diluted to 6 mg/ml using 20 mM Hepes pH 7.5, 50 mM NaCl. The ligand of interest was dissolved in DMSO to 10 mM and then diluted into the protein solution to a final concentration of 1 mM. The ligand was then allowed to incubate with the protein for two hours at room temperature prior to dispensing plates. The drop composition was 0.15 ul protein ligand solution, 0.3 ul 11% (v/v) PEG 4K, 0.1 M MES pH 6.5, and 0.05 ul Mpro crystal seed stock. The Mpro crystal seed stock was prepared by crushing Mpro crystals with a pipette tip, suspending them in 30% PEG 4K, 5% (v/v) DMSO, 0.1 M MES pH 6.5, and vortexing for 60 s with approximately 10 glass beads (1.0 mm diameter, BioSpec products). Reservoir solution was 11pc (v/v) PEG 4K, 5pc (v/v) DMSO, 0.1 M MES pH 6.5. Crystals were grown using the sitting drop vapor diffusion method at 20 degrees C and appeared within 24 hours, reaching full size within 36 hours. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.9126 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Jun 12, 2020 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9126 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.3→55.51 Å / Num. obs: 62149 / % possible obs: 97.2 % / Redundancy: 10.1 % / CC1/2: 0.996 / Rmerge(I) obs: 0.199 / Rpim(I) all: 0.066 / Rrim(I) all: 0.209 / Net I/σ(I): 10.7 / Num. measured all: 627154 / Scaling rejects: 3375 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5r8t Resolution: 1.3→47.93 Å / Cor.coef. Fo:Fc: 0.979 / Cor.coef. Fo:Fc free: 0.97 / WRfactor Rfree: 0.1868 / WRfactor Rwork: 0.1463 / FOM work R set: 0.8576 / SU B: 2.228 / SU ML: 0.04 / SU R Cruickshank DPI: 0.0543 / SU Rfree: 0.0511 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.054 / ESU R Free: 0.051 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.3 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 62.55 Å2 / Biso mean: 14.721 Å2 / Biso min: 6.26 Å2
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Refinement step | Cycle: final / Resolution: 1.3→47.93 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.3→1.334 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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