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Yorodumi- PDB-8f44: Crystal structure of SARS-CoV-2 3CL protease in complex with a di... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8f44 | |||||||||
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Title | Crystal structure of SARS-CoV-2 3CL protease in complex with a dimethyl phenyl sulfane inhibitor | |||||||||
Components | 3C-like proteinase | |||||||||
Keywords | HYDROLASE/Inhibitor / HYDROLASE / HYDROLASE-Inhibitor complex | |||||||||
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 / host cell endosome / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / 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 / host cell Golgi apparatus / methyltransferase cap1 / symbiont-mediated perturbation of host ubiquitin-like protein modification / mRNA (nucleoside-2'-O-)-methyltransferase activity / DNA helicase / 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 / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / 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: 1.65 Å | |||||||||
Authors | Liu, L. / Lovell, S. / Cooper, A. / Battaile, K.P. / Dampalla, C.S. / Groutas, W.C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2023 Title: Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and ...Title: Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV). Authors: Dampalla, C.S. / Miller, M.J. / Kim, Y. / Zabiegala, A. / Nguyen, H.N. / Madden, T.K. / Thurman, H.A. / Machen, A.J. / Cooper, A. / Liu, L. / Battaile, K.P. / Lovell, S. / Chang, K.O. / Groutas, W.C. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8f44.cif.gz | 139.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f44.ent.gz | 107.2 KB | Display | PDB format |
PDBx/mmJSON format | 8f44.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8f44_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8f44_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8f44_validation.xml.gz | 28 KB | Display | |
Data in CIF | 8f44_validation.cif.gz | 40 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f4/8f44 ftp://data.pdbj.org/pub/pdb/validation_reports/f4/8f44 | HTTPS FTP |
-Related structure data
Related structure data | 8e5xC 8e5zC 8e61C 8e63C 8e64C 8e65C 8e68C 8e69C 8e6aC 8e6bC 8e6cC 8e6dC 8e6eC 8f45C 8f46C 6xmkS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 34068.805 Da / Num. of mol.: 2 / Fragment: Full Length Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: rep, 1a-1b / Plasmid: pET-28 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: P0DTD1, SARS coronavirus main proteinase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-PG4 / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.27 Å3/Da / Density % sol: 45.74 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 20% (w/v) PEG 2,000 MME, 100 mM Tris, 200 mM Trimethylamine N-oxide dihydrate |
-Data collection
Diffraction | Mean temperature: 291 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: NSLS-II / Beamline: 19-ID / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS EIGER2 XE 9M / Detector: PIXEL / Date: Oct 30, 2022 |
Radiation | Monochromator: Double Crystal Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.65→98.93 Å / Num. obs: 72855 / % possible obs: 99.9 % / Redundancy: 5.7 % / CC1/2: 0.999 / Rmerge(I) obs: 0.062 / Rpim(I) all: 0.028 / Rrim(I) all: 0.069 / Χ2: 0.92 / Net I/σ(I): 12.2 / Num. measured all: 417393 |
Reflection shell | Resolution: 1.65→1.69 Å / % possible obs: 100 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.834 / Num. measured all: 33281 / Num. unique obs: 5397 / CC1/2: 0.805 / Rpim(I) all: 0.361 / Rrim(I) all: 0.911 / Χ2: 0.85 / Net I/σ(I) obs: 1.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6XMK Resolution: 1.65→56.35 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 23.29 / 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.65→56.35 Å
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Refine LS restraints |
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LS refinement shell |
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