[English] 日本語
Yorodumi- PDB-8dd9: Crystal Structure of SARS-CoV-2 Main Protease (Mpro) S144L Mutant... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dd9 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal Structure of SARS-CoV-2 Main Protease (Mpro) S144L Mutant in Complex with Inhibitor GC376 | ||||||
Components | 3C-like proteinase nsp5 | ||||||
Keywords | VIRAL PROTEIN / Protease / SARS-CoV-2 / Mpro | ||||||
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 / 5'-3' DNA helicase activity / SARS coronavirus main proteinase / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease 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 / 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 / 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: 2.04 Å | ||||||
Authors | Lewandowski, E.M. / Jacobs, L.M.C. / Hu, Y. / Tan, H. / Wang, J. / Chen, Y. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Acs Cent.Sci. / Year: 2023 Title: Naturally Occurring Mutations of SARS-CoV-2 Main Protease Confer Drug Resistance to Nirmatrelvir. Authors: Hu, Y. / Lewandowski, E.M. / Tan, H. / Zhang, X. / Morgan, R.T. / Zhang, X. / Jacobs, L.M.C. / Butler, S.G. / Gongora, M.V. / Choy, J. / Deng, X. / Chen, Y. / Wang, J. #1: Journal: Biorxiv / Year: 2022 Title: Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. Authors: Hu, Y. / Lewandowski, E.M. / Tan, H. / Zhang, X. / Morgan, R.T. / Zhang, X. / Jacobs, L.M.C. / Butler, S.G. / Gongora, M.V. / Choy, J. / Deng, X. / Chen, Y. / Wang, J. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8dd9.cif.gz | 140.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8dd9.ent.gz | 108 KB | Display | PDB format |
PDBx/mmJSON format | 8dd9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dd/8dd9 ftp://data.pdbj.org/pub/pdb/validation_reports/dd/8dd9 | HTTPS FTP |
---|
-Related structure data
Related structure data | 8dczC 8dd1C 8dfeC 8dfnC 8dgbC 7lyhS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
Unit cell |
| ||||||||||||
Components on special symmetry positions |
|
-Components
#1: Protein | Mass: 33851.625 Da / Num. of mol.: 1 / Mutation: S144L 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 |
---|---|
#2: Chemical | ChemComp-B1S / ( |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 1.98 Å3/Da / Density % sol: 37.82 % |
---|---|
Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, hanging drop Details: 25% PEG 3350, 0.1M Potassium/Sodium Tartrate, 0.005M Magnesium Chloride |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 4, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.04→50 Å / Num. obs: 16416 / % possible obs: 96.9 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.097 / Net I/σ(I): 13.59 |
Reflection shell | Resolution: 2.04→2.08 Å / Rmerge(I) obs: 0.509 / Mean I/σ(I) obs: 2.31 / Num. unique obs: 827 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7LYH Resolution: 2.04→38.92 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.924 / SU B: 10 / SU ML: 0.139 / Cross valid method: THROUGHOUT / ESU R: 0.258 / ESU R Free: 0.199 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 1 Å / Shrinkage radii: 1 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 99.92 Å2 / Biso mean: 34.05 Å2 / Biso min: 16.74 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.04→38.92 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.042→2.095 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: 12.086 Å / Origin y: -0.023 Å / Origin z: 4.494 Å
|