[English] 日本語
Yorodumi
- PDB-7n8c: Joint X-ray/neutron structure of SARS-CoV-2 main protease (Mpro) ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7n8c
TitleJoint X-ray/neutron structure of SARS-CoV-2 main protease (Mpro) in complex with Mcule5948770040
Components3C-like proteinase
KeywordsHYDROLASE / cysteine protease / inhibitor complex / protonation states
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 / snRNP Assembly / TRAF3-dependent IRF activation pathway / Replication of the SARS-CoV-2 genome / double membrane vesicle viral factory outer membrane / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / SARS coronavirus main proteinase / host cell endosome / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / : / 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 / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / copper ion binding / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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
RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / : / Coronavirus Nsp12 Interface domain profile. ...RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / : / Coronavirus Nsp12 Interface domain profile. / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / NSP14, guanine-N7-methyltransferase domain, coronavirus / NSP12 RNA-dependent RNA polymerase, coronavirus / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / Nidovirus 2-O-methyltransferase / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Nidovirus 3'-5' exoribonuclease domain / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Nonstructural protein 13, 1B domain, coronavirus / Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain / 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 / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) 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 / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Endoribonuclease EndoU-like / NendoU domain, nidovirus / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / DNA2/NAM7 helicase-like, C-terminal / AAA domain / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / Lipocalin signature. / 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. / Coronavirus 3Ecto domain profile. / : / Betacoronavirus Nsp3e group 2-specific marker (G2M) domain profile. / NSP1, C-terminal domain, betacoronavirus / 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 / Betacoronavirus (BetaCoV) Nsp1 C-terminal 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 superfamily, betacoronavirus / Non-structural protein 6, betacoronavirus / Betacoronavirus nucleic acid-binding (NAB) / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Non-structural protein NSP3A domain-like superfamily / Papain-like protease, N-terminal domain superfamily, coronavirus / Papain-like viral protease, palm and finger domains, coronavirus / : / Coronavirus (CoV) Nsp2 middle domain profile. / Coronavirus (CoV) Nsp2 N-terminal domain profile. / Coronavirus (CoV) Nsp2 C-terminal domain profile. / NSP1, globular domain, alpha/betacoronavirus / : / Coronavirus (CoV) Nsp3 Y domain profile. / Coronavirus (CoV) Nsp1 globular domain profile. / Coronavirus replicase NSP2, N-terminal / Nonstructural protein 2, N-terminal domain, coronavirus / Coronavirus replicase NSP2, C-terminal / Non-structural protein 2, C-terminal domain, coronavirus / Coronavirus Nsp3a Ubl domain profile. / Coronavirus Nsp3d Ubl domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp7 cofactor domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp8 cofactor domain profile. / Coronavirus Nsp9 single-stranded RNA (ssRNA)-binding domain profile. / Coronavirus (CoV) ExoN/MTase coactivator domain profile. / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / NSP3, second ubiquitin-like (Ubl) domain, coronavirus
Similarity search - Domain/homology
DEUTERATED WATER / Chem-YD1 / Replicase polyprotein 1ab
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / NEUTRON DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsKovalevsky, A. / Kneller, D.W. / Coates, L.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Structural, Electronic, and Electrostatic Determinants for Inhibitor Binding to Subsites S1 and S2 in SARS-CoV-2 Main Protease.
Authors: Kneller, D.W. / Li, H. / Galanie, S. / Phillips, G. / Labbe, A. / Weiss, K.L. / Zhang, Q. / Arnould, M.A. / Clyde, A. / Ma, H. / Ramanathan, A. / Jonsson, C.B. / Head, M.S. / Coates, L. / ...Authors: Kneller, D.W. / Li, H. / Galanie, S. / Phillips, G. / Labbe, A. / Weiss, K.L. / Zhang, Q. / Arnould, M.A. / Clyde, A. / Ma, H. / Ramanathan, A. / Jonsson, C.B. / Head, M.S. / Coates, L. / Louis, J.M. / Bonnesen, P.V. / Kovalevsky, A.
History
DepositionJun 14, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 23, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 10, 2021Group: Database references / Category: citation / citation_author / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Dec 22, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3C-like proteinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,1952
Polymers33,8261
Non-polymers3691
Water1,78399
1
A: 3C-like proteinase
hetero molecules

A: 3C-like proteinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,3904
Polymers67,6512
Non-polymers7382
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_455-x-1,y,-z1
Unit cell
Length a, b, c (Å)55.314, 81.301, 88.578
Angle α, β, γ (deg.)90.00, 96.46, 90.00
Int Tables number5
Space group name H-MI121
Components on special symmetry positions
IDModelComponents
11A-521-

DOD

21A-564-

DOD

31A-599-

DOD

-
Components

#1: Protein 3C-like proteinase / 3CL-PRO / 3CLp / Main protease / Mpro / Non-structural protein 5 / nsp5 / SARS coronavirus main proteinase


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
#2: Chemical ChemComp-YD1 / 6-[4-(3,4-dichlorophenyl)piperazin-1-yl]carbonyl-1~{H}-pyrimidine-2,4-dione


Mass: 369.203 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H14Cl2N4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-DOD / water / Heavy water


Mass: 18.015 Da / Num. of mol.: 99 / Source method: isolated from a natural source / Formula: D2O / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

Experiment
MethodNumber of used crystals
X-RAY DIFFRACTION1
NEUTRON DIFFRACTION1

-
Sample preparation

CrystalDensity Matthews: 2.93 Å3/Da / Density % sol: 57.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 18% PEG3350, 0.1 M Bis-Tris pH 7.0 reservoir solution and 0.2 microL microseeds at 1:200 dilution

-
Data collection

Diffraction
IDMean temperature (K)Crystal-IDSerial crystal experiment
12931N
22931N
Diffraction source
SourceSiteBeamlineTypeIDWavelength (Å)
ROTATING ANODERIGAKU MICROMAX-007 HF11.54
SPALLATION SOURCEORNL Spallation Neutron Source MANDI22.00-4.16
Detector
TypeIDDetectorDateDetails
DECTRIS EIGER R 4M1PIXELMar 10, 2021OSMIC VARIMAX
ORNL ANGER CAMERA2AREA DETECTORMar 3, 2021COLLIMATORS
Radiation
IDMonochromatorProtocolMonochromatic (M) / Laue (L)Scattering typeWavelength-ID
1NONESINGLE WAVELENGTHMx-ray1
2NONELAUELneutron2
Radiation wavelength
IDWavelength (Å)Relative weight
11.541
221
34.161
Reflection

Entry-ID: 7N8C

Resolution (Å)Num. obs% possible obs (%)Redundancy (%)CC1/2Rmerge(I) obsRpim(I) allDiffraction-IDNet I/σ(I)
2.2-59.721910896.34.70.9920.1070.055111.4
2.5-12.861153485.65.50.9460.2120.096215.6
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Diffraction-ID% possible all
2.2-2.274.80.6021.618840.686194.7
2.5-2.595.60.2835.81176288.4

-
Processing

Software
NameVersionClassification
nCNS1.0.0refinement
CrysalisProdata reduction
CrysalisProdata scaling
PHASERphasing
nCNSphasing
Mantiddata reduction
LAUENORMdata scaling
Refinement

Biso max: 101.48 Å2 / Biso mean: 44.13 Å2 / Biso min: 18.84 Å2 / % reflection Rfree: 5 % / R Free selection details: RANDOM / Cross valid method: FREE R-VALUE / σ(F): 2.5 / Method to determine structure: MOLECULAR REPLACEMENT / Stereochemistry target values: Joint X-ray/neutron ML / Solvent model: CNS bulk solvent model used / Bsol: 51.4773 Å2 / ksol: 0.317191 e/Å3

Starting modelResolution (Å)Refine-IDRfactor RfreeRfactor Rfree errorRfactor RworkNum. reflection RfreeNum. reflection RworkNum. reflection obs% reflection obs (%)
7LTJ

7ltj

2.2-25.9X-RAY DIFFRACTION0.1920.0070.177856159571747688.1
2.5-12.86NEUTRON DIFFRACTION0.2110.0090.187577109551153284.9
Refine analyze
Refine-ID#notag 0
X-RAY DIFFRACTION
FreeObs
Luzzati coordinate error0.260.23
Luzzati d res low-5
Luzzati sigma a0.230.25
Luzzati d res high-2.2
NEUTRON DIFFRACTION
FreeObs
Luzzati coordinate error0.290.25
Luzzati d res low-5
Luzzati sigma a0.30.27
Luzzati d res high-2.5
Refine funct minimized
Refine-IDType
X-RAY DIFFRACTIONJoint X-ray/neutron ML
NEUTRON DIFFRACTIONJoint X-ray/neutron ML
Refinement stepCycle: LAST / Resolution: 2.2→25.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2368 0 24 99 2491
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.008
X-RAY DIFFRACTIONx_angle_deg1.1
X-RAY DIFFRACTIONx_torsion_deg27.1
X-RAY DIFFRACTIONx_torsion_impr_deg0.86
NEUTRON DIFFRACTIONx_bond_d0.008
NEUTRON DIFFRACTIONx_angle_deg1.1
NEUTRON DIFFRACTIONx_torsion_deg27.1
NEUTRON DIFFRACTIONx_torsion_impr_deg0.86
LS refinement shell

Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection Rfree% reflection Rfree (%)Rfactor RworkNum. reflection RworkRefine-IDRfactor Rfree errorNum. reflection allNum. reflection obs% reflection obs (%)
2.2-2.30.2548850.2421515X-RAY DIFFRACTION0.0272448160365.5
2.3-2.420.239814.50.2431708X-RAY DIFFRACTION0.0272458178972.8
2.42-2.570.2331045.30.2191851X-RAY DIFFRACTION0.0232480195578.8
2.57-2.770.271014.80.2122001X-RAY DIFFRACTION0.0272481210284.7
2.77-3.050.2331145.10.2062131X-RAY DIFFRACTION0.0222483224590.4
3.05-3.490.2081134.90.1872183X-RAY DIFFRACTION0.022462229693.3
3.49-4.390.1691305.40.1512266X-RAY DIFFRACTION0.0152494239696.1
4.39-25.90.151255.20.1472302X-RAY DIFFRACTION0.0132539242795.6
2.5-2.610.2577550.2291417NEUTRON DIFFRACTION0.031700149287.8
2.61-2.750.2447250.2211379NEUTRON DIFFRACTION0.0291659145187.5
2.75-2.920.245755.10.2241401NEUTRON DIFFRACTION0.0281688147687.4
2.92-3.140.237805.50.1951369NEUTRON DIFFRACTION0.0271669144986.8
3.14-3.450.235624.20.1961410NEUTRON DIFFRACTION0.031676147287.8
3.45-3.940.202845.60.1711404NEUTRON DIFFRACTION0.0221697148887.7
3.94-4.920.172694.70.151386NEUTRON DIFFRACTION0.0211692145586
4.92-12.860.178604.80.1821189NEUTRON DIFFRACTION0.0231708124973.1

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more