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- PDB-6wrh: The crystal structure of Papain-Like Protease of SARS CoV-2 , C11... -

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Basic information

Entry
Database: PDB / ID: 6wrh
TitleThe crystal structure of Papain-Like Protease of SARS CoV-2 , C111S mutant
ComponentsNon-structural protein 3
KeywordsHYDROLASE / covid-19 / coronavirus / SARS / CoV-2 / papain-like protease / IDP51000 / Center for Structural Genomics of Infectious Diseases / CSGID
Function / homology
Function and homology information


protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity ...protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / snRNP Assembly / Replication of the SARS-CoV-2 genome / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / host cell endoplasmic reticulum-Golgi intermediate compartment / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / 5'-3' DNA helicase activity / 3'-5'-RNA exonuclease activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / omega peptidase activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / host cell Golgi apparatus / symbiont-mediated suppression of host NF-kappaB cascade / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / regulation of autophagy / host cell perinuclear region of cytoplasm / viral protein processing / lyase activity / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / copper ion binding / viral translational frameshifting / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / 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
Papain-like viral protease, N-terminal domain / Papain-like viral protease, thumb domain / Jelly Rolls - #1680 / Helicase, Ruva Protein; domain 3 / Ubiquitin-like (UB roll) / RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus ...Papain-like viral protease, N-terminal domain / Papain-like viral protease, thumb domain / Jelly Rolls - #1680 / Helicase, Ruva Protein; domain 3 / Ubiquitin-like (UB roll) / RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / NSP14, guanine-N7-methyltransferase domain, coronavirus / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / NSP12 RNA-dependent RNA polymerase, coronavirus / : / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Coronavirus Nsp12 Interface domain profile. / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / Nidovirus 2-O-methyltransferase / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Non-structural protein NSP15, N-terminal domain superfamily, coronavirus / Non-structural protein NSP15, middle domain superfamily / Coronavirus replicase NSP15, N-terminal oligomerization / Nonstructural protein 15, middle domain, coronavirus / Nonstructural protein 13, 1B domain, coronavirus / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Nidovirus 3'-5' exoribonuclease domain / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Non-structural protein NSP16, coronavirus-like / Non-structural protein 14, coronavirus / RNA polymerase, N-terminal, coronavirus / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) domain profile. / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Endoribonuclease EndoU-like / NendoU domain, nidovirus / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / : / Lipocalin signature. / DNA2/NAM7 helicase-like, C-terminal / AAA domain / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / Non-structural protein NSP3, SUD-N (Mac2) domain, betacoronavirus / Sarbecovirus Nsp3c-N domain profile. / Non-structural protein NSP3, N-terminal, betacoronavirus / Polyprotein cleavage domain PL2pro superfamily, betacoronavirus / Non-structural protein NSP3, SUD-N (Mac2) domain superfamily, betacoronavirus / Betacoronavirus SUD-C domain / Betacoronavirus replicase NSP3, N-terminal / NSP1 globular domain superfamily, betacoronavirus / Non-structural protein 2, SARS-CoV-like / Carbamoyl-phosphate synthase subdomain signature 2. / Betacoronavirus Nsp3c-M domain profile. / NSP1, globular domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus / Betacoronavirus replicase NSP1 / Betacoronavirus single-stranded poly(A) binding domain / NSP1, C-terminal domain, betacoronavirus / : / Betacoronavirus (BetaCoV) Nsp1 C-terminal domain profile. / Betacoronavirus Nsp3e group 2-specific marker (G2M) domain profile. / Betacoronavirus Nsp3c-C domain profile. / Betacoronavirus Nsp3e nucleic acid-binding (NAB) domain profile. / DPUP/SUD, C-terminal, betacoronavirus / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Non-structural protein NSP3A domain-like superfamily / Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus / Non-structural protein 6, betacoronavirus / Betacoronavirus nucleic acid-binding (NAB) / Papain-like viral protease, palm and finger domains, coronavirus / Papain-like protease, N-terminal domain superfamily, coronavirus / Coronavirus replicase NSP2, N-terminal / : / Coronavirus replicase NSP2, C-terminal / Coronavirus (CoV) Nsp2 middle domain profile. / NSP1, globular domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp1 globular domain profile. / Coronavirus (CoV) Nsp2 N-terminal domain profile. / Coronavirus (CoV) Nsp2 C-terminal domain profile. / Nonstructural protein 2, N-terminal domain, coronavirus / Non-structural protein 2, C-terminal domain, coronavirus / NSP3, second ubiquitin-like (Ubl) domain, coronavirus / Coronavirus Nsp3a Ubl domain profile. / Coronavirus Nsp3d Ubl domain profile. / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / Peptidase family C16 domain profile.
Similarity search - Domain/homology
PHOSPHATE ION / Replicase polyprotein 1ab
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsOsipiuk, J. / Tesar, C. / Jedrzejczak, R. / Endres, M. / Welk, L. / Babnigg, G. / Kim, Y. / Michalska, K. / Joachimiak, A. / Center for Structural Genomics of Infectious Diseases (CSGID)
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HHSN272201200026C United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HHSN272201700060C United States
CitationJournal: Nat Commun / Year: 2021
Title: Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors.
Authors: Osipiuk, J. / Azizi, S.A. / Dvorkin, S. / Endres, M. / Jedrzejczak, R. / Jones, K.A. / Kang, S. / Kathayat, R.S. / Kim, Y. / Lisnyak, V.G. / Maki, S.L. / Nicolaescu, V. / Taylor, C.A. / ...Authors: Osipiuk, J. / Azizi, S.A. / Dvorkin, S. / Endres, M. / Jedrzejczak, R. / Jones, K.A. / Kang, S. / Kathayat, R.S. / Kim, Y. / Lisnyak, V.G. / Maki, S.L. / Nicolaescu, V. / Taylor, C.A. / Tesar, C. / Zhang, Y.A. / Zhou, Z. / Randall, G. / Michalska, K. / Snyder, S.A. / Dickinson, B.C. / Joachimiak, A.
History
DepositionApr 29, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 6, 2020Provider: repository / Type: Initial release
Revision 1.1Jun 10, 2020Group: Structure summary / Category: entity / entity_name_com
Item: _entity.details / _entity.pdbx_description ..._entity.details / _entity.pdbx_description / _entity.pdbx_ec / _entity_name_com.name
Revision 1.2Jan 27, 2021Group: Structure summary / Category: entity / entity_name_com / Item: _entity.pdbx_ec / _entity_name_com.name
Revision 1.3Feb 10, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.4Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Non-structural protein 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,5339
Polymers35,9281
Non-polymers6058
Water6,846380
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: assembly as a monomer was assigned based on crystal packing of molecules in this deposit and 6W9C PDB deposition for wild-type enzyme
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1080 Å2
ΔGint-28 kcal/mol
Surface area15700 Å2
Unit cell
Length a, b, c (Å)82.403, 82.403, 134.503
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221

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Components

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Protein , 1 types, 1 molecules A

#1: Protein Non-structural protein 3 / Peptidase C16 / Papain-like protease / pp1ab / ORF1ab polyprotein / nsp3 / PL2-PRO / Papain-like ...Peptidase C16 / Papain-like protease / pp1ab / ORF1ab polyprotein / nsp3 / PL2-PRO / Papain-like proteinase / PL-PRO


Mass: 35927.695 Da / Num. of mol.: 1 / Mutation: C111S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: rep, 1a-1b / Plasmid: pMCSG53 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P0DTD1, EC: 3.4.19.121, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases

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Non-polymers , 5 types, 388 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: PO4
#4: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 380 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.67 Å3/Da / Density % sol: 66.48 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 4.5 / Details: 0.1 M Acetate buffer, 0.8 M NaH2PO4 / 1.2 M K2HPO4

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.9792 Å
DetectorType: DECTRIS PILATUS3 X 6M / Detector: PIXEL / Date: Apr 28, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 1.6→48.99 Å / Num. obs: 69708 / % possible obs: 99.1 % / Redundancy: 13.7 % / Rmerge(I) obs: 0.095 / Rpim(I) all: 0.025 / Rrim(I) all: 0.098 / Χ2: 1.421 / Net I/av σ(I): 34.8 / Net I/σ(I): 6.8
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.6-1.638.30.8171.7131050.7410.2930.8710.59689.5
1.63-1.669.30.70132570.810.2360.7420.63293.8
1.66-1.6910.90.65134220.8780.2040.6840.64898.4
1.69-1.7213.50.59834600.9070.1690.6220.725100
1.72-1.7613.80.5234990.9280.1450.540.778100
1.76-1.8140.43734870.9430.1210.4540.904100
1.8-1.8514.10.37634680.9610.1030.391.011100
1.85-1.914.20.31234810.9710.0850.3231.182100
1.9-1.9513.40.26735070.9750.0750.2781.35699.9
1.95-2.0215.20.23234780.9830.0610.241.544100
2.02-2.0915.10.20834840.9860.0550.2151.693100
2.09-2.17150.18735140.9880.050.1941.829100
2.17-2.2714.50.1734930.9890.0450.1761.869100
2.27-2.3913.70.15135150.9910.0420.1571.8699.8
2.39-2.5415.30.13935180.9930.0360.1431.833100
2.54-2.7415.10.12535130.9940.0330.131.861100
2.74-3.0114.20.10735570.9960.0290.1111.82699.9
3.01-3.4515.10.08935650.9960.0230.0921.798100
3.45-4.3414.60.07236160.9980.0190.0751.72999.9
4.34-48.99140.05437690.9990.0150.0561.52299.8

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Processing

Software
NameVersionClassification
HKL-3000data scaling
REFMAC5.8.0258refinement
PDB_EXTRACT3.25data extraction
HKL-3000data reduction
HKL-3000phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6W9C

6w9c


Resolution: 1.6→48.99 Å / Cor.coef. Fo:Fc: 0.981 / Cor.coef. Fo:Fc free: 0.966 / SU B: 2.308 / SU ML: 0.035 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.056 / ESU R Free: 0.057
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1643 3516 5 %RANDOM
Rwork0.1234 ---
obs0.1255 66140 98.98 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 92.83 Å2 / Biso mean: 28.527 Å2 / Biso min: 18.39 Å2
Baniso -1Baniso -2Baniso -3
1--0.07 Å2-0.03 Å2-0 Å2
2---0.07 Å20 Å2
3---0.21 Å2
Refinement stepCycle: final / Resolution: 1.6→48.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2507 0 30 380 2917
Biso mean--40.43 42.61 -
Num. residues----316
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0132697
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172426
X-RAY DIFFRACTIONr_angle_refined_deg1.4331.6583682
X-RAY DIFFRACTIONr_angle_other_deg1.4271.5735687
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0175348
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.18823.835133
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.8815471
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.253159
X-RAY DIFFRACTIONr_chiral_restr0.0710.2360
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.023016
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02547
X-RAY DIFFRACTIONr_rigid_bond_restr2.46935122
LS refinement shellResolution: 1.6→1.641 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.265 199 -
Rwork0.223 4425 -
all-4624 -
obs--89.3 %

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