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Yorodumi- PDB-8e5c: Crystal Structure of SARS CoV-2 Mpro mutant L50F with Nirmatrelvi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8e5c | ||||||
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Title | Crystal Structure of SARS CoV-2 Mpro mutant L50F with Nirmatrelvir captured in two conformational states | ||||||
Components | 3C-like proteinase nsp5 | ||||||
Keywords | VIRAL PROTEIN / HYDROLASE/INHIBITOR / Coronavirus / COVID-19 / COVID / PROTEASE / DRUG RESISTANCE / COMPLEX / HYDROLASE / DURG DISCOVERY / MAIN PROTEASE / MPRO / SUBSTRATE COMPLEX / Pfizer IV compound / L50F / Nirmatrelvir / VIRAL PROTEIN-HYDROLASE-INHIBITOR complex / 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 / 5'-3' DNA helicase activity / snRNP Assembly / double membrane vesicle viral factory outer membrane / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / SARS coronavirus main proteinase / host cell endosome / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / symbiont-mediated degradation of host mRNA / symbiont-mediated suppression of host toll-like receptor signaling pathway / 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 / virus-mediated perturbation of host defense response / viral RNA genome replication / cysteine-type endopeptidase activity / 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 | Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Shaqra, A.M. / Schiffer, C.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Acs Infect Dis. / Year: 2024 Title: Contributions of Hyperactive Mutations in M pro from SARS-CoV-2 to Drug Resistance. Authors: Flynn, J.M. / Zvornicanin, S.N. / Tsepal, T. / Shaqra, A.M. / Kurt Yilmaz, N. / Jia, W. / Moquin, S. / Dovala, D. / Schiffer, C.A. / Bolon, D.N.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8e5c.cif.gz | 86.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8e5c.ent.gz | 61 KB | Display | PDB format |
PDBx/mmJSON format | 8e5c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e5/8e5c ftp://data.pdbj.org/pub/pdb/validation_reports/e5/8e5c | HTTPS FTP |
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-Related structure data
Related structure data | 8dt9C 8e4wC 7l0dS 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 on special symmetry positions |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 33859.562 Da / Num. of mol.: 1 / Mutation: L50F 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 (E. coli) References: UniProt: P0DTD1, SARS coronavirus main proteinase |
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-Non-polymers , 5 types, 325 molecules
#2: Chemical | ChemComp-DMS / | ||||
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#3: Chemical | ChemComp-4WI / ( | ||||
#4: Chemical | ChemComp-NA / #5: Chemical | ChemComp-CL / #6: Water | ChemComp-HOH / | |
-Details
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: 2.24 Å3/Da / Density % sol: 44.97 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: 10-20 % (w/v) PEG 3350, 0.20-0.30 M NaCl, and 0.1 M Bis-Tris methane pH 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.54178 Å |
Detector | Type: RIGAKU HyPix-6000HE / Detector: PIXEL / Date: Apr 15, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→25.41 Å / Num. obs: 16012 / % possible obs: 99.82 % / Redundancy: 2 % / Biso Wilson estimate: 17.1 Å2 / CC1/2: 0.988 / CC star: 0.997 / Rmerge(I) obs: 0.08596 / Rpim(I) all: 0.08696 / Rrim(I) all: 0.1216 / Net I/σ(I): 7.25 |
Reflection shell | Resolution: 2.2→2.279 Å / Redundancy: 2 % / Rmerge(I) obs: 0.3643 / Mean I/σ(I) obs: 1.95 / Num. unique obs: 1546 / CC1/2: 0.707 / CC star: 0.91 / Rpim(I) all: 0.3643 / Rrim(I) all: 0.5152 / % possible all: 99.55 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7L0D Resolution: 2.2→25.41 Å / SU ML: 0.2797 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 23.8808 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: 17.67 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2→25.41 Å
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Refine LS restraints |
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LS refinement shell |
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