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Yorodumi- PDB-7z3u: Crystal structure of SARS-CoV-2 Main Protease after incubation wi... -
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-Basic information
Entry | Database: PDB / ID: 7z3u | ||||||||||||||||||
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Title | Crystal structure of SARS-CoV-2 Main Protease after incubation with Sulfo-Calpeptin | ||||||||||||||||||
Components |
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Keywords | HYDROLASE / main protease / MPro / cystein protease / drug development / drug target / peptide-like inhibitor / SARS-CoV-2 / COVID-19 | ||||||||||||||||||
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 / symbiont-mediated suppression of host NF-kappaB cascade / 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 / 3'-5'-RNA exonuclease activity / SARS coronavirus main proteinase / host cell endoplasmic reticulum-Golgi intermediate compartment / 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 / viral protein processing / host cell endoplasmic reticulum membrane / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / viral translational frameshifting / 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 synthetic construct (others) | ||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.72 Å | ||||||||||||||||||
Authors | Reinke, P.Y.A. / Falke, S. / Lieske, J. / Ewert, W. / Loboda, J. / Rahmani Mashhour, A. / Hauser, M. / Karnicar, K. / Usenik, A. / Lindic, N. ...Reinke, P.Y.A. / Falke, S. / Lieske, J. / Ewert, W. / Loboda, J. / Rahmani Mashhour, A. / Hauser, M. / Karnicar, K. / Usenik, A. / Lindic, N. / Lach, M. / Boehler, H. / Beck, T. / Cox, R. / Chapman, H.N. / Hinrichs, W. / Turk, D. / Guenther, S. / Meents, A. | ||||||||||||||||||
Funding support | Germany, Slovenia, 5items
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Citation | Journal: Commun Biol / Year: 2023 Title: Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections. Authors: Reinke, P.Y.A. / de Souza, E.E. / Gunther, S. / Falke, S. / Lieske, J. / Ewert, W. / Loboda, J. / Herrmann, A. / Rahmani Mashhour, A. / Karnicar, K. / Usenik, A. / Lindic, N. / Sekirnik, A. ...Authors: Reinke, P.Y.A. / de Souza, E.E. / Gunther, S. / Falke, S. / Lieske, J. / Ewert, W. / Loboda, J. / Herrmann, A. / Rahmani Mashhour, A. / Karnicar, K. / Usenik, A. / Lindic, N. / Sekirnik, A. / Botosso, V.F. / Santelli, G.M.M. / Kapronezai, J. / de Araujo, M.V. / Silva-Pereira, T.T. / Filho, A.F.S. / Tavares, M.S. / Florez-Alvarez, L. / de Oliveira, D.B.L. / Durigon, E.L. / Giaretta, P.R. / Heinemann, M.B. / Hauser, M. / Seychell, B. / Bohler, H. / Rut, W. / Drag, M. / Beck, T. / Cox, R. / Chapman, H.N. / Betzel, C. / Brehm, W. / Hinrichs, W. / Ebert, G. / Latham, S.L. / Guimaraes, A.M.S. / Turk, D. / Wrenger, C. / Meents, A. #1: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2012 Title: Towards automated crystallographic structure refinement with phenix.refine. Authors: Afonine, P.V. / Grosse-Kunstleve, R.W. / Echols, N. / Headd, J.J. / Moriarty, N.W. / Mustyakimov, M. / Terwilliger, T.C. / Urzhumtsev, A. / Zwart, P.H. / Adams, P.D. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7z3u.cif.gz | 275 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7z3u.ent.gz | 206.9 KB | Display | PDB format |
PDBx/mmJSON format | 7z3u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7z3u_validation.pdf.gz | 459.8 KB | Display | wwPDB validaton report |
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Full document | 7z3u_full_validation.pdf.gz | 464.6 KB | Display | |
Data in XML | 7z3u_validation.xml.gz | 28.8 KB | Display | |
Data in CIF | 7z3u_validation.cif.gz | 42 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z3/7z3u ftp://data.pdbj.org/pub/pdb/validation_reports/z3/7z3u | HTTPS FTP |
-Related structure data
Related structure data | 7qgwC 7qkaC 7qkbC 7qkcC 7z3tC 7z58C 8c3dC 6ynqS 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
-Protein / Protein/peptide , 2 types, 4 molecules ABFG
#1: Protein | Mass: 33873.547 Da / Num. of mol.: 2 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: Protein/peptide | Type: Peptide-like / Class: Inhibitor / Mass: 362.464 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (synth.) synthetic construct (others) / References: BIRD: PRD_002387 |
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-Non-polymers , 4 types, 440 molecules
#3: Chemical | #4: Chemical | #5: Chemical | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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Nonpolymer details | The bound form of calpeptin (RN2) in this entry was derived by incubation of MPro with the ...The bound form of calpeptin (RN2) in this entry was derived by incubation of MPro with the precursor Sulfo-Calpeptin, a modified form of calpeptin that is sulfonated at its C-terminus to mask the aldehyde group. |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.54 Å3/Da / Density % sol: 51.62 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion Details: Co-crystallization with the compound was achieved by equlibrating a 6.25 mg/ml protein solution in 20 mM HEPES buffer (pH 7.8) containing 1 mM DTT, 1mM EDTA, and 150 mM NaCl against a ...Details: Co-crystallization with the compound was achieved by equlibrating a 6.25 mg/ml protein solution in 20 mM HEPES buffer (pH 7.8) containing 1 mM DTT, 1mM EDTA, and 150 mM NaCl against a reservoir solution of 100 mM MIB buffer (2:3:3 molar ratio of malonic acid, imidazole, and boric acid), pH 7.5, containing 25% v/v PEG 1500 and 5% v/v DMSO. Prior to crystallization compound solutions in DMSO were dried onto the wells of SwissCI 96-well plates. To achieve reproducible crystal growth seeding was used. Crystals appeared within a few hours and reached their final size after 2 -3 days. Crystals were manually harvested and flash cooled in liquid nitrogen for subsequent X-ray diffraction data collection. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, DESY / Beamline: P11 / Wavelength: 1.033 Å |
Detector | Type: DECTRIS EIGER2 S 16M / Detector: PIXEL / Date: May 7, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033 Å / Relative weight: 1 |
Reflection | Resolution: 1.72→49.22 Å / Num. obs: 74689 / % possible obs: 99.7 % / Redundancy: 7.5 % / Biso Wilson estimate: 26.42 Å2 / CC1/2: 0.999 / CC star: 1 / Rmerge(I) obs: 0.101 / Rpim(I) all: 0.039 / Rrim(I) all: 0.1086 / Net I/σ(I): 12.54 |
Reflection shell | Resolution: 1.72→1.782 Å / Redundancy: 7.7 % / Rmerge(I) obs: 2.172 / Mean I/σ(I) obs: 0.95 / Num. unique obs: 7314 / CC1/2: 0.524 / CC star: 0.829 / Rpim(I) all: 0.8283 / Rrim(I) all: 2.328 / % possible all: 98.31 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6YNQ Resolution: 1.72→49.22 Å / SU ML: 0.2558 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 28.6145 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 38.76 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.72→49.22 Å
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Refine LS restraints |
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LS refinement shell |
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