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Yorodumi- PDB-7lco: Improved Feline Drugs as SARS-CoV-2 Mpro Inhibitors: Structure-Ac... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7lco | |||||||||
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Title | Improved Feline Drugs as SARS-CoV-2 Mpro Inhibitors: Structure-Activity Studies & Micellar Solubilization for Enhanced Bioavailability | |||||||||
Components | 3C-like proteinase | |||||||||
Keywords | VIRAL PROTEIN / HYDROLASE/INHIBITOR / COVID-19 / SARS-CoV-2 / 3CLpro / coronavirus / main protease / kinetics / SARS / Hydrolase-Hydrolase Inhibitor complex / 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 / SARS coronavirus main proteinase / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / symbiont-mediated suppression of host NF-kappaB cascade / 5'-3' DNA helicase activity / 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 / mRNA (guanine-N7)-methyltransferase / omega peptidase activity / methyltransferase cap1 / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / host cell Golgi apparatus / 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 / host cell perinuclear region of cytoplasm / single-stranded RNA binding / host cell endoplasmic reticulum membrane / viral protein processing / lyase activity / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / viral translational frameshifting / RNA-directed RNA polymerase / copper ion binding / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / lipid binding / DNA-templated transcription / 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: 1.9 Å | |||||||||
Authors | Khan, M.B. / Lu, J. / Arutyunova, E. / Young, H.S. / Lemieux, M.J. | |||||||||
Funding support | Canada, 2items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2021 Title: Improved SARS-CoV-2 M pro inhibitors based on feline antiviral drug GC376: Structural enhancements, increased solubility, and micellar studies. Authors: Vuong, W. / Fischer, C. / Khan, M.B. / van Belkum, M.J. / Lamer, T. / Willoughby, K.D. / Lu, J. / Arutyunova, E. / Joyce, M.A. / Saffran, H.A. / Shields, J.A. / Young, H.S. / Nieman, J.A. / ...Authors: Vuong, W. / Fischer, C. / Khan, M.B. / van Belkum, M.J. / Lamer, T. / Willoughby, K.D. / Lu, J. / Arutyunova, E. / Joyce, M.A. / Saffran, H.A. / Shields, J.A. / Young, H.S. / Nieman, J.A. / Tyrrell, D.L. / Lemieux, M.J. / Vederas, J.C. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7lco.cif.gz | 227.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lco.ent.gz | 152.6 KB | Display | PDB format |
PDBx/mmJSON format | 7lco.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7lco_validation.pdf.gz | 731.9 KB | Display | wwPDB validaton report |
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Full document | 7lco_full_validation.pdf.gz | 739.7 KB | Display | |
Data in XML | 7lco_validation.xml.gz | 15.6 KB | Display | |
Data in CIF | 7lco_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lc/7lco ftp://data.pdbj.org/pub/pdb/validation_reports/lc/7lco | HTTPS FTP |
-Related structure data
Related structure data | 7lcrC 7lcsC 7lctC 7ldlC 6wtmS 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: 33825.547 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 O103:H2 (bacteria) / Strain (production host): 12009 References: UniProt: P0DTD1, SARS coronavirus main proteinase |
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#2: Chemical | ChemComp-XTJ / ( |
#3: 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: 2.01 Å3/Da / Density % sol: 38.84 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop Details: 0.2 M Sodium chloride, 0.1 M HEPES pH 7.0, 20 % w/v PEG 6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08B1-1 / Wavelength: 1.52127 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Sep 21, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.52127 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→39.05 Å / Num. obs: 20533 / % possible obs: 95.76 % / Redundancy: 6.57 % / Biso Wilson estimate: 39.49 Å2 / CC1/2: 0.999 / Net I/σ(I): 22.66 |
Reflection shell | Resolution: 1.9→1.968 Å / Num. unique obs: 1980 / CC1/2: 0.654 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6WTM Resolution: 1.9→39.05 Å / SU ML: 0.3627 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 31.0312 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 45.16 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→39.05 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: -16.9450332788 Å / Origin y: 14.2992614146 Å / Origin z: 17.3083472772 Å
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Refinement TLS group | Selection details: all |