[English] 日本語
Yorodumi- PDB-8uif: Crystal structure of SARS CoV-2 3CL protease in complex with GSK4... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8uif | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of SARS CoV-2 3CL protease in complex with GSK4365096A | ||||||
Components | 3C-like proteinase nsp5 | ||||||
Keywords | HYDROLASE / 3CL protease / SARS / viral protein | ||||||
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 endosome / host cell endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / 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 / 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: 2.02 Å | ||||||
Authors | Concha, N.O. / Williams, S.P. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2024 Title: Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement. Authors: Barton, L.S. / Callahan, J.F. / Cantizani, J. / Concha, N.O. / Cotillo Torrejon, I. / Goodwin, N.C. / Joshi-Pangu, A. / Kiesow, T.J. / McAtee, J.J. / Mellinger, M. / Nixon, C.J. / Padron- ...Authors: Barton, L.S. / Callahan, J.F. / Cantizani, J. / Concha, N.O. / Cotillo Torrejon, I. / Goodwin, N.C. / Joshi-Pangu, A. / Kiesow, T.J. / McAtee, J.J. / Mellinger, M. / Nixon, C.J. / Padron-Barthe, L. / Patterson, J.R. / Pearson, N.D. / Pouliot, J.J. / Rendina, A.R. / Buitrago Santanilla, A. / Schneck, J.L. / Sanz, O. / Thalji, R.K. / Ward, P. / Williams, S.P. / King, B.W. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8uif.cif.gz | 422.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8uif.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8uif.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uif_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8uif_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8uif_validation.xml.gz | 25.1 KB | Display | |
Data in CIF | 8uif_validation.cif.gz | 35 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ui/8uif ftp://data.pdbj.org/pub/pdb/validation_reports/ui/8uif | HTTPS FTP |
-Related structure data
Related structure data | 8uhoC 8uiaC 8uldC C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Unit cell |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Ens-ID: ens_1
|
-Components
#1: Protein | Mass: 33825.547 Da / Num. of mol.: 2 / Fragment: UNP residues 3264-3569 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 | Mass: 625.727 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H44FN3O7 / Feature type: SUBJECT OF INVESTIGATION #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: 2.6 Å3/Da / Density % sol: 52.71 % |
---|---|
Crystal grow | Temperature: 295 K / Method: vapor diffusion / Details: 0.1M HEPES, pH 7.5, 16% PEG8000, 0.1M KH2PO4 |
-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 EIGER2 S 16M / Detector: PIXEL / Date: Feb 24, 2021 |
Radiation | Monochromator: Graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.02→100 Å / Num. obs: 45983 / % possible obs: 90.1 % / Redundancy: 5.3 % / Biso Wilson estimate: 24.65 Å2 / CC1/2: 0.986 / Rmerge(I) obs: 0.122 / Rpim(I) all: 0.057 / Rrim(I) all: 0.135 / Net I/σ(I): 7.3 |
Reflection shell | Resolution: 2.65→2.7 Å / Rmerge(I) obs: 0.91 / Num. unique obs: 957 / CC1/2: 0.47 / Rpim(I) all: 0.454 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.02→41.02 Å / SU ML: 0.19 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 20.9091 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.08 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.02→41.02 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | Type: Torsion NCS / Rms dev position: 0.787532426548 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: -2.21786685349 Å / Origin y: -2.8000120648 Å / Origin z: 16.1303962099 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group | Selection details: all |