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Yorodumi- PDB-7z4s: Crystal structure of SARS-CoV-2 Mpro in complex with cyclic pepti... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7z4s | |||||||||||||||
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Title | Crystal structure of SARS-CoV-2 Mpro in complex with cyclic peptide GM4 including unnatural amino acids. | |||||||||||||||
Components |
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Keywords | UNKNOWN FUNCTION / protease | |||||||||||||||
Function / homology | Function and homology information viral genome replication / methyltransferase 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 / Replication of the SARS-CoV-2 genome / methylation / double membrane vesicle viral factory outer membrane ...viral genome replication / methyltransferase 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 / Replication of the SARS-CoV-2 genome / methylation / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / host cell endosome / 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 / host cell Golgi apparatus / symbiont-mediated perturbation of host ubiquitin-like protein modification / endonuclease 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 / induction by virus of host autophagy / symbiont-mediated suppression of host gene expression / cysteine-type endopeptidase activity / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / SARS-CoV-2 activates/modulates innate and adaptive immune responses / proteolysis / zinc ion binding / membrane Similarity search - Function | |||||||||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 synthetic construct (others) | |||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | |||||||||||||||
Authors | Owen, C.D. / Miura, T. / Malla, T. / Lukacik, L. / Strain-Damerell, C.M. / Tumber, A. / Brewitz, L. / McDonough, M.A. / Salah, E. / Terasaka, N. ...Owen, C.D. / Miura, T. / Malla, T. / Lukacik, L. / Strain-Damerell, C.M. / Tumber, A. / Brewitz, L. / McDonough, M.A. / Salah, E. / Terasaka, N. / Katoh, T. / Kawamura, A. / Schofield, C.J. / Suga, H. / Walsh, M.A. | |||||||||||||||
Funding support | 1items
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Citation | Journal: Nat.Chem. / Year: 2023 Title: In vitro selection of macrocyclic peptide inhibitors containing cyclic gamma 2,4 -amino acids targeting the SARS-CoV-2 main protease. Authors: Miura, T. / Malla, T.R. / Owen, C.D. / Tumber, A. / Brewitz, L. / McDonough, M.A. / Salah, E. / Terasaka, N. / Katoh, T. / Lukacik, P. / Strain-Damerell, C. / Mikolajek, H. / Walsh, M.A. / ...Authors: Miura, T. / Malla, T.R. / Owen, C.D. / Tumber, A. / Brewitz, L. / McDonough, M.A. / Salah, E. / Terasaka, N. / Katoh, T. / Lukacik, P. / Strain-Damerell, C. / Mikolajek, H. / Walsh, M.A. / Kawamura, A. / Schofield, C.J. / Suga, H. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7z4s.cif.gz | 269.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7z4s.ent.gz | 216.3 KB | Display | PDB format |
PDBx/mmJSON format | 7z4s.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z4/7z4s ftp://data.pdbj.org/pub/pdb/validation_reports/z4/7z4s | HTTPS FTP |
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-Related structure data
Related structure data | 6yb7S 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
-Protein / Protein/peptide , 2 types, 4 molecules ABCD
#1: Protein | Mass: 33841.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Production host: Escherichia coli (E. coli) References: UniProt: P0DTC1, SARS coronavirus main proteinase #2: Protein/peptide | Mass: 1562.817 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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-Non-polymers , 5 types, 298 molecules
#3: Chemical | #4: Chemical | ChemComp-DMS / | #5: Chemical | #6: Chemical | ChemComp-PGE / | #7: Water | ChemComp-HOH / | |
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-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: 2.34 Å3/Da / Density % sol: 47.56 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 Details: Mpro was thawed and diluted to 6 mg/ml using 20 mM Hepes pH 7.5, 50 mM NaCl. GM4 was diluted into the protein solution to a final concentration of 10 mM and allowed to incubate for two hours ...Details: Mpro was thawed and diluted to 6 mg/ml using 20 mM Hepes pH 7.5, 50 mM NaCl. GM4 was diluted into the protein solution to a final concentration of 10 mM and allowed to incubate for two hours at room temperature prior to dispensing plates. The drop composition was 0.15 ul protein ligand solution, 0.3 ul 11% (v/v) PEG 4K, 0.1 M MES pH 6.5, and 0.05 ul Mpro crystal seed stock. The Mpro crystal seed stock was prepared by crushing Mpro crystals with a pipette tip, suspending them in 30% PEG 4K, 5% (v/v) DMSO, 0.1 M MES pH 6.5, and vortexing for 60 s with approximately 10 glass beads (1.0 mm diameter, BioSpec products). Reservoir solution was 11% (v/v) PEG 4K, 5% (v/v) DMSO, 0.1 M MES pH 6.5. Crystals were grown using the sitting drop vapor diffusion method at 20 C and appeared within 24 hours, reaching full size within 36 hours. Crystals were looped after one week. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9762 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 11, 2021 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9762 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 1.7→53.23 Å / Num. obs: 407784 / % possible obs: 99.9 % / Redundancy: 5.9 % / CC1/2: 0.998 / Rmerge(I) obs: 0.129 / Rpim(I) all: 0.058 / Net I/σ(I): 6.6 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6yb7 Resolution: 1.7→53.23 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.952 / SU B: 8.294 / SU ML: 0.123 / Cross valid method: THROUGHOUT / ESU R: 0.118 / ESU R Free: 0.115 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY
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Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.1 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.483 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→53.23 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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