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Yorodumi- PDB-7uup: SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with Nirma... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7uup | |||||||||
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Title | SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with Nirmatrelvir (PF-07321332) | |||||||||
Components | 3C-like proteinase nsp5 | |||||||||
Keywords | VIRAL PROTEIN / SARSCoV2 / SARS-CoV-2 / coronavirus / Main Protease / Protease / Mpro / S144A / mutant / resistance / 3C-like proteinase / CL3pro / Inhibitor / Complex / Covalent / Adduct / Nirmatrelvir / PF-07321332 / Nitrile / Peptidomimetic | |||||||||
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 endosome / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / 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 endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / RNA helicase / induction by virus of host autophagy / copper ion binding / RNA-directed RNA polymerase / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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 / molecular replacement / Resolution: 2 Å | |||||||||
Authors | Westberg, M. / Fernandez, D. / Lin, M.Z. | |||||||||
Funding support | Denmark, 2items
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Citation | Journal: Sci Transl Med / Year: 2024 Title: An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations. Authors: Westberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. / Lo, C.W. / Karim, M. / Ning, L. / Beck, A. / Saenkham-Huntsinger, P. ...Authors: Westberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. / Lo, C.W. / Karim, M. / Ning, L. / Beck, A. / Saenkham-Huntsinger, P. / Tat, V. / Drelich, A. / Peng, B.H. / Einav, S. / Tseng, C.K. / Blish, C. / Lin, M.Z. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7uup.cif.gz | 78.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7uup.ent.gz | 56.1 KB | Display | PDB format |
PDBx/mmJSON format | 7uup.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uu/7uup ftp://data.pdbj.org/pub/pdb/validation_reports/uu/7uup | HTTPS FTP |
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-Related structure data
Related structure data | 7setC 7sf1C 7sf3C 7u92C 7uugC 8ezvC 8ezzC 8f02C 8f2cC 8f2dC 6lzeS C: citing same article (ref.) S: Starting model for refinement |
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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
#1: Protein | Mass: 33809.547 Da / Num. of mol.: 1 / Mutation: S144A 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) / Strain (production host): T7 Express LysY/Iq References: UniProt: P0DTD1, SARS coronavirus main proteinase |
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#2: Chemical | ChemComp-4WI / ( |
#3: Chemical | ChemComp-CL / |
#4: 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: 2.26 Å3/Da / Density % sol: 45.59 % |
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Crystal grow | Temperature: 289.15 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: Sitting drops consisted of 0.19 uL A:0.19 uL B: A) 5.1 mg/mL Mpro S144A + 0.9 mM ML1001 in in 20 mM Tris pH 7.3 + 3 mM TCEP + 3 % DMSO B) 0.1 M MES pH 6.5, 10% PEG20000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 8, 2022 Details: Flat Si Rh coated M0, Kirkpatrick-Baez flat bent Si M1 & M2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Liquid nitrogen-cooled double crystal, non fixed exit slit Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2→105.16 Å / Num. all: 21186 / Num. obs: 21186 / % possible obs: 99.2 % / Redundancy: 3.6 % / Rpim(I) all: 0.057 / Rrim(I) all: 0.112 / Rsym value: 0.095 / Net I/av σ(I): 6.5 / Net I/σ(I): 7.8 / Num. measured all: 77254 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6LZE Resolution: 2→35.08 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.946 / SU B: 6.068 / SU ML: 0.158 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.194 / ESU R Free: 0.171 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 109.78 Å2 / Biso mean: 39.098 Å2 / Biso min: 22.02 Å2
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Refinement step | Cycle: final / Resolution: 2→35.08 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.052 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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