+Open data
-Basic information
Entry | Database: PDB / ID: 8ute | ||||||
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Title | Structure of SARS-Cov2 3CLPro in complex with Compound 27 | ||||||
Components | 3C-like proteinase nsp5 | ||||||
Keywords | VIRAL PROTEIN / HYDROLASE/INHIBITOR / 3CL Pro / MPro / inhibitor / HYDROLASE-INHIBITOR complex | ||||||
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 endoplasmic reticulum-Golgi intermediate compartment / 3'-5'-RNA exonuclease activity / symbiont-mediated suppression of host NF-kappaB cascade / 5'-3' DNA helicase 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 / mRNA (guanine-N7)-methyltransferase / omega peptidase activity / methyltransferase cap1 / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / host cell Golgi apparatus / 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 / host cell perinuclear region of cytoplasm / single-stranded RNA binding / host cell endoplasmic reticulum membrane / viral protein processing / lyase activity / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / viral translational frameshifting / RNA-directed RNA polymerase / copper ion binding / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / lipid binding / DNA-templated transcription / 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: 1.45 Å | ||||||
Authors | Krishnamurthy, H. / Zhuang, N. / Qiang, D. / Wu, Y. / Klein, D.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Invention of MK-7845, a SARS-CoV-2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic. Authors: Shurtleff, V.W. / Layton, M.E. / Parish, C.A. / Perkins, J.J. / Schreier, J.D. / Wang, Y. / Adam, G.C. / Alvarez, N. / Bahmanjah, S. / Bahnck-Teets, C.M. / Boyce, C.W. / Burlein, C. / ...Authors: Shurtleff, V.W. / Layton, M.E. / Parish, C.A. / Perkins, J.J. / Schreier, J.D. / Wang, Y. / Adam, G.C. / Alvarez, N. / Bahmanjah, S. / Bahnck-Teets, C.M. / Boyce, C.W. / Burlein, C. / Cabalu, T.D. / Campbell, B.T. / Carroll, S.S. / Chang, W. / de Lera Ruiz, M. / Dolgov, E. / Fay, J.F. / Fox, N.G. / Goh, S.L. / Hartingh, T.J. / Hurzy, D.M. / Kelly 3rd, M.J. / Klein, D.J. / Klingler, F.M. / Krishnamurthy, H. / Kudalkar, S. / Mayhood, T.W. / McKenna, P.M. / Murray, E.M. / Nahas, D. / Nawrat, C.C. / Park, S. / Qian, D. / Roecker, A.J. / Sharma, V. / Shipe, W.D. / Su, J. / Taggart, R.V. / Truong, Q. / Wu, Y. / Zhou, X. / Zhuang, N. / Perlin, D.S. / Olsen, D.B. / Howe, J.A. / McCauley, J.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ute.cif.gz | 85.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ute.ent.gz | 62.3 KB | Display | PDB format |
PDBx/mmJSON format | 8ute.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ute_validation.pdf.gz | 812.9 KB | Display | wwPDB validaton report |
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Full document | 8ute_full_validation.pdf.gz | 814.2 KB | Display | |
Data in XML | 8ute_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | 8ute_validation.cif.gz | 24.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ut/8ute ftp://data.pdbj.org/pub/pdb/validation_reports/ut/8ute | HTTPS FTP |
-Related structure data
Related structure data | 8upsC 8upvC 8upwC C: citing same article (ref.) |
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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: 33825.547 Da / Num. of mol.: 1 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 | ||||
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#2: Chemical | ChemComp-XKQ / Mass: 518.594 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H40F2N4O6 / Feature type: SUBJECT OF INVESTIGATION | ||||
#3: Chemical | ChemComp-EDO / #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: 2.73 Å3/Da / Density % sol: 54.86 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1 M sodium cacodylate pH 6, 40% v/v MPD, 5% w/v PEG 3350 in a 1:1 ratio of protein to precipitant solution |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08B1-1 / Wavelength: 1.18053 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Jan 15, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.18053 Å / Relative weight: 1 |
Reflection | Resolution: 1.45→44.55 Å / Num. obs: 63750 / % possible obs: 99.4 % / Redundancy: 4 % / CC1/2: 1 / Rmerge(I) obs: 0.026 / Rpim(I) all: 0.015 / Rrim(I) all: 0.03 / Χ2: 0.91 / Net I/σ(I): 20.8 / Num. measured all: 257569 |
Reflection shell | Resolution: 1.45→1.47 Å / % possible obs: 97.9 % / Redundancy: 4 % / Rmerge(I) obs: 0.665 / Num. measured all: 12440 / Num. unique obs: 3099 / CC1/2: 0.852 / Rpim(I) all: 0.372 / Rrim(I) all: 0.765 / Χ2: 0.91 / Net I/σ(I) obs: 2.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.45→44.55 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.957 / SU R Cruickshank DPI: 0.07 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.072 / SU Rfree Blow DPI: 0.071 / SU Rfree Cruickshank DPI: 0.07 Details: HYDROGENS WERE FULLY REFINED WITH ZERO OCCUPANCY AT NUCLEAR POSITION.
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Displacement parameters | Biso mean: 28.61 Å2
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Refine analyze | Luzzati coordinate error obs: 0.21 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 1.45→44.55 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.45→1.46 Å / Total num. of bins used: 51
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