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- PDB-7lcr: Improved Feline Drugs as SARS-CoV-2 Mpro Inhibitors: Structure-Ac... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7lcr | |||||||||
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Title | Improved Feline Drugs as SARS-CoV-2 Mpro Inhibitors: Structure-Activity Studies & Micellar Solubilization for Enhanced Bioavailability | |||||||||
![]() | 3C-like proteinase | |||||||||
![]() | 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 | ![]() 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 | ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Khan, M.B. / Arutyunova, E. / Young, H.S. / Lemieux, M.J. | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 427.9 KB | Display | ![]() |
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PDB format | ![]() | 294.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7lcoC ![]() 7lcsC ![]() 7lctC ![]() 7ldlC ![]() 6wtmS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: SER / Beg label comp-ID: SER / End auth comp-ID: GLN / End label comp-ID: GLN / Auth seq-ID: 1 - 306 / Label seq-ID: 1 - 306
NCS oper: (Code: givenMatrix: (-0.251812410942, -0.68393256832, 0.684709246095), (-0.679293175271, -0.379022330123, -0.628412965571), (0.68931218742, -0.623360501845, -0.369148199256)Vector: 11. ...NCS oper: (Code: given Matrix: (-0.251812410942, -0.68393256832, 0.684709246095), Vector: |
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Components
#1: Protein | Mass: 33825.547 Da / Num. of mol.: 2 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: Chemical | #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.62 Å3/Da / Density % sol: 52.98 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop / pH: 7 Details: 0.2 M Magnesium chloride hexahydrate, 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: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Sep 12, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→38 Å / Num. obs: 99833 / % possible obs: 99.82 % / Redundancy: 13.06 % / Biso Wilson estimate: 35.65 Å2 / CC1/2: 0.997 / Net I/σ(I): 8.1 |
Reflection shell | Resolution: 1.95→2.02 Å / Num. unique obs: 5191 / CC1/2: 0.562 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6WTM Resolution: 1.95→38 Å / SU ML: 0.4457 / Cross valid method: FREE R-VALUE / σ(F): 1.18 / Phase error: 38.8817 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: 66 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.95→38 Å
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Refine LS restraints |
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Refine LS restraints NCS | Type: Torsion NCS / Rms dev position: 3.2535350909 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 1.87122744762 Å / Origin y: -2.87622878478 Å / Origin z: -16.0163672939 Å
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Refinement TLS group | Selection details: all |