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Yorodumi- PDB-9at6: Crystal structure of SARS-CoV-2 3CL protease in complex with a me... -
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-Basic information
Entry | Database: PDB / ID: 9at6 | |||||||||
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Title | Crystal structure of SARS-CoV-2 3CL protease in complex with a methylbicyclo[2.2.1]heptene 2-pyrrolidone inhibitor | |||||||||
Components | 3C-like proteinase nsp5 | |||||||||
Keywords | HYDROLASE/INHIBITOR / protease / Severe Acute Respiratory Syndrome Coronavirus 2 / SARS-COV-2 3CL protease inhibitors / Covid-19 / viral protein / 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 / symbiont-mediated suppression of host NF-kappaB cascade / 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 / 3'-5'-RNA exonuclease activity / SARS coronavirus main proteinase / 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 / viral protein processing / host cell endoplasmic reticulum membrane / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / viral translational frameshifting / 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: 1.4 Å | |||||||||
Authors | Lovell, S. / Cooper, A. / Battaile, K.P. / Dampalla, C.S. / Groutas, W.C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Structure-Guided Design of Potent Coronavirus Inhibitors with a 2-Pyrrolidone Scaffold: Biochemical, Crystallographic, and Virological Studies. Authors: Dampalla, C.S. / Kim, Y. / Zabiegala, A. / Howard, D.J. / Nguyen, H.N. / Madden, T.K. / Thurman, H.A. / 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 | 9at6.cif.gz | 259.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9at6.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 9at6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9at6_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 9at6_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 9at6_validation.xml.gz | 27 KB | Display | |
Data in CIF | 9at6_validation.cif.gz | 40.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/at/9at6 ftp://data.pdbj.org/pub/pdb/validation_reports/at/9at6 | HTTPS FTP |
-Related structure data
Related structure data | 9asvC 9aswC 9asyC 9aszC 9at0C 9at1C 9at3C 9at4C 9at5C 9at7C 9ataC 9atdC 9ateC 9atfC 9atgC 9athC 9atiC 9atjC 9atsC 9attC 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: 33921.629 Da / Num. of mol.: 2 / Fragment: UNP residues 3264-3567 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 | Mass: 598.709 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H42N4O9S #3: Chemical | Mass: 598.709 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H42N4O9S #4: Chemical | ChemComp-PG4 / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | Has protein modification | 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: 2.24 Å3/Da / Density % sol: 45.17 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7 Details: 20% w/v PEG3350, 100 mM Bis-Tris propane, pH 7.0, 20 mM sodium potassium phosphate |
-Data collection
Diffraction | Mean temperature: 100 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 5, 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: 1.4→49.14 Å / Num. obs: 116866 / % possible obs: 99.6 % / Redundancy: 6.9 % / CC1/2: 1 / Rmerge(I) obs: 0.048 / Rpim(I) all: 0.019 / Rrim(I) all: 0.051 / Χ2: 1.01 / Net I/σ(I): 16.5 / Num. measured all: 808746 |
Reflection shell | Resolution: 1.4→1.42 Å / % possible obs: 99 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.983 / Num. measured all: 35314 / Num. unique obs: 5729 / CC1/2: 0.756 / Rpim(I) all: 0.429 / Rrim(I) all: 1.075 / Χ2: 1.06 / Net I/σ(I) obs: 1.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.4→49.14 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.03 / Phase error: 18.41 / 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: 1.4→49.14 Å
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Refine LS restraints |
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LS refinement shell |
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