[English] 日本語

- PDB-7aeg: SARS-CoV-2 main protease in a covalent complex with SDZ 224015 de... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 7aeg | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | SARS-CoV-2 main protease in a covalent complex with SDZ 224015 derivative, compound 5 | |||||||||
![]() |
| |||||||||
![]() | VIRAL PROTEIN / covid-19 / inhibitor / protease | |||||||||
Function / homology | ![]() 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 ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment / double membrane vesicle viral factory outer membrane / 3'-5'-RNA exonuclease activity / SARS coronavirus main proteinase / 5'-3' DNA helicase activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / symbiont-mediated suppression of host toll-like receptor signaling pathway / G-quadruplex RNA binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / omega peptidase activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / host cell Golgi apparatus / symbiont-mediated suppression of host NF-kappaB cascade / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / single-stranded 3'-5' DNA helicase activity / double-stranded DNA helicase activity / forked DNA-dependent helicase activity / four-way junction helicase activity / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / cysteine-type deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / host cell perinuclear region of cytoplasm / regulation of autophagy / viral protein processing / lyase activity / 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 | ![]() ![]() ![]() | |||||||||
![]() | 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. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 83.7 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 60.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 327 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 327.2 KB | Display | |
Data in XML | ![]() | 15 KB | Display | |
Data in CIF | ![]() | 21.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7aehC ![]() 5r8tS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|
1 | ![]()
| |||||||||
Unit cell |
| |||||||||
Components on special symmetry positions |
|
-
Components
#1: Protein | Mass: 33697.418 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: rep, 1a-1b / Production host: ![]() ![]() References: UniProt: P0DTD1, SARS coronavirus main proteinase | ||||||
---|---|---|---|---|---|---|---|
#2: Protein/peptide | | ||||||
#3: Chemical | ChemComp-DMS / #4: Water | ChemComp-HOH / | Has ligand of interest | Y | Has protein modification | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 1.93 Å3/Da / Density % sol: 36.32 % / Description: square plates |
---|---|
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 | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Jul 29, 2020 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.999 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.7→54.98 Å / Num. obs: 28892 / % possible obs: 99.9 % / Redundancy: 6.2 % / CC1/2: 0.985 / Rmerge(I) obs: 0.224 / Rpim(I) all: 0.099 / Rrim(I) all: 0.245 / Net I/σ(I): 7.6 / Num. measured all: 178201 / Scaling rejects: 2546 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
|
-
Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 5r8t Resolution: 1.7→54.98 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.939 / SU B: 2.638 / SU ML: 0.084 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.115 / ESU R Free: 0.11 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 207.1 Å2 / Biso mean: 18.033 Å2 / Biso min: 4.59 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.7→54.98 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.7→1.744 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
|