[English] 日本語
Yorodumi
- PDB-7tdu: Joint X-ray/neutron structure of SARS-CoV-2 main protease (3CL Mp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7tdu
TitleJoint X-ray/neutron structure of SARS-CoV-2 main protease (3CL Mpro) in complex with BBH-1
Components3C-like proteinase
KeywordsHYDROLASE/INHIBITOR / SARS-CoV-2 main protease / homodimer / cysteine protease / covalent inhibitor / HYDROLASE / 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 / TRAF3-dependent IRF activation pathway / Translation of Replicase and Assembly of the Replication Transcription Complex / 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 / 5'-3' DNA helicase activity / symbiont-mediated suppression of host NF-kappaB cascade / 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 / copper ion binding / RNA-directed RNA polymerase / viral translational frameshifting / 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
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 Nonstructural protein 13, 1B domain ...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 Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / Coronavirus Nsp12 Interface domain profile. / NSP12 RNA-dependent RNA polymerase, coronavirus / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) 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 / Nidovirus 2-O-methyltransferase / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Non-structural protein NSP16, coronavirus-like / Non-structural protein 14, coronavirus / RNA polymerase, N-terminal, coronavirus / Nidovirus 3'-5' exoribonuclease domain / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / 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 / 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 / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / 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 / NSP1, globular domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp2 middle domain profile. / 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 / : / Coronavirus 3Ecto domain profile. / NSP3, second ubiquitin-like (Ubl) domain, coronavirus / Coronavirus Nsp3a Ubl domain profile. / Coronavirus Nsp3d Ubl domain profile. / : / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / Coronavirus (CoV) Nsp3 Y domain profile. / Coronavirus replicase NSP7 / Peptidase family C16 domain profile.
Similarity search - Domain/homology
DEUTERATED WATER / Chem-I1W / Replicase polyprotein 1ab
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / NEUTRON DIFFRACTION / NUCLEAR REACTOR / MOLECULAR REPLACEMENT / Resolution: 1.85 Å
AuthorsKovalevsky, A. / Kneller, D.W. / Coates, L.
Funding support1items
OrganizationGrant numberCountry
Not funded
Citation
Journal: Nat Commun / Year: 2022
Title: Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease
Authors: Kneller, D.W. / Li, H. / Phillips, G. / Weiss, K.L. / Zhang, Q. / Arnould, M.A. / Jonsson, C.B. / Surendranathan, S. / Parvathareddy, J. / Blakeley, M.P. / Coates, L. / Louis, J.M. / ...Authors: Kneller, D.W. / Li, H. / Phillips, G. / Weiss, K.L. / Zhang, Q. / Arnould, M.A. / Jonsson, C.B. / Surendranathan, S. / Parvathareddy, J. / Blakeley, M.P. / Coates, L. / Louis, J.M. / Bonnesen, P.V. / Kovalevsky, A.
#1: Journal: Res Sq / Year: 2022
Title: Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease: room-temperature X-ray and neutron crystallography, binding thermodynamics, and antiviral activity.
Authors: Kneller, D. / Li, H. / Phillips, G. / Weiss, K. / Zhang, Q. / Arnould, M. / Jonsson, C. / Surendranathan, S. / Parvathareddy, J. / Blakeley, M. / Coates, L. / Louis, J. / Bonnesen, P. / Kovalevsky, A.
#2: Journal: Acta Cryst. / Year: 2009
Title: Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures for biological macromolecules
Authors: Adams, P.D. / Mustyakimov, M. / Afonine, P.V. / Langan, P.
History
DepositionJan 3, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 2, 2022Provider: repository / Type: Initial release
Revision 1.1May 4, 2022Group: Database references / Category: citation / citation_author
Revision 1.2Apr 3, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3C-like proteinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4662
Polymers33,8261
Non-polymers6411
Water2,648147
1
A: 3C-like proteinase
hetero molecules

A: 3C-like proteinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,9334
Polymers67,6512
Non-polymers1,2822
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Unit cell
Length a, b, c (Å)55.020, 81.217, 88.825
Angle α, β, γ (deg.)90.00, 96.72, 90.00
Int Tables number5
Space group name H-MI121
Components on special symmetry positions
IDModelComponents
11A-524-

DOD

21A-543-

DOD

31A-603-

DOD

-
Components

#1: Protein 3C-like proteinase / 3CL-PRO / 3CLP / Main protease / Mpro


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-I1W / (1R,2S,5S)-N-{(1S,2S)-1-(1,3-benzothiazol-2-yl)-1-hydroxy-3-[(3S)-2-oxo(1-~2~H)pyrrolidin-3-yl]propan-2-yl}-3-{N-[tert-butyl(~2~H)carbamoyl]-3-methyl-L-(N-~2~H)valyl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-(~2~H)carboxamide


Mass: 640.836 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C33H48N6O5S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-DOD / water


Mass: 18.015 Da / Num. of mol.: 147 / Source method: isolated from a natural source / Formula: D2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

Experiment
MethodNumber of used crystals
X-RAY DIFFRACTION1
NEUTRON DIFFRACTION1

-
Sample preparation

CrystalDensity Matthews: 2.91 Å3/Da / Density % sol: 57.78 %
Crystal growTemperature: 287 K / Method: vapor diffusion, sitting drop / pH: 6.6 / Details: 20% PEG3350, 0.1 M Bis-Tris pH 6.5

-
Data collection

Diffraction
IDMean temperature (K)Crystal-IDSerial crystal experiment
12931N
22931N
Diffraction source
SourceSiteBeamlineTypeIDWavelength (Å)
ROTATING ANODERIGAKU MICROMAX-007 HF11.54
NUCLEAR REACTORILL LADI III23.0-4.0
Detector
TypeIDDetectorDateDetails
DECTRIS EIGER R 4M1PIXELOct 11, 2021OSMIC VARIMAX
MAATEL2IMAGE PLATEOct 5, 2021COLLIMATORS
Radiation
IDMonochromatorProtocolMonochromatic (M) / Laue (L)Scattering typeWavelength-ID
1NONESINGLE WAVELENGTHMx-ray1
2NONELAUELneutron2
Radiation wavelength
IDWavelength (Å)Relative weight
11.541
231
341
Reflection

Entry-ID: 7TDU

Resolution (Å)Num. obs% possible obs (%)Redundancy (%)Rmerge(I) obsDiffraction-IDNet I/σ(I)CC1/2Rpim(I) all
1.85-59.753201396.65.40.076113.6
2.2-44.041547178.73.10.16127.90.9860.094
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsDiffraction-ID% possible allCC1/2Rpim(I) all
1.85-1.925.40.6711.43127194.2
2.2-2.322.90.3672.11840264.20.8250.223

-
Processing

Software
NameVersionClassification
nCNS1.0.0refinement
CrysalisProdata reduction
CrysalisProdata scaling
PHASERphasing
nCNSphasing
LAUEGENdata reduction
LSCALEdata scaling
Refinement

Biso max: 94.84 Å2 / Biso mean: 33.86 Å2 / Biso min: 10.39 Å2 / Cross valid method: FREE R-VALUE / Method to determine structure: MOLECULAR REPLACEMENT / Starting model: 7N8C

7n8c

/ Stereochemistry target values: Joint X-ray/neutron ML / Solvent model: CNS bulk solvent model used

Resolution (Å)Refine-IDRfactor RfreeRfactor Rfree errorRfactor RworkNum. reflection RfreeNum. reflection RworkNum. reflection allNum. reflection obs% reflection Rfree (%)% reflection obs (%)Bsol (Å2)ksol (e/Å3)
1.85-29.88X-RAY DIFFRACTION0.210.0060.19714152728933147287044.986.649.8120.311508
2.2-29.9NEUTRON DIFFRACTION0.2570.010.237652124081976013060566.132.01040.537435
Refine analyze
Refine-ID#notag 0
X-RAY DIFFRACTION
FreeObs
Luzzati coordinate error0.240.22
Luzzati d res low-5
Luzzati sigma a0.210.21
Luzzati d res high-1.85
NEUTRON DIFFRACTION
FreeObs
Luzzati coordinate error0.390.34
Luzzati d res low-5
Luzzati sigma a0.770.74
Luzzati d res high-2.2
Refine funct minimized
Refine-IDType
X-RAY DIFFRACTIONJoint X-ray/neutron ML
NEUTRON DIFFRACTIONJoint X-ray/neutron ML
Refinement stepCycle: LAST / Resolution: 1.85→29.88 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2368 0 45 147 2560
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.011
X-RAY DIFFRACTIONx_angle_deg1.2
X-RAY DIFFRACTIONx_torsion_deg29.4
X-RAY DIFFRACTIONx_torsion_impr_deg0.88
NEUTRON DIFFRACTIONx_bond_d0.011
NEUTRON DIFFRACTIONx_angle_deg1.2
NEUTRON DIFFRACTIONx_torsion_deg29.4
NEUTRON DIFFRACTIONx_torsion_impr_deg0.88
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 (%)
1.85-1.930.2481254.80.2552494X-RAY DIFFRACTION0.0224139261963.3
1.93-2.040.2471655.30.2452926X-RAY DIFFRACTION0.0194105309175.3
2.04-2.160.2871694.90.2453295X-RAY DIFFRACTION0.0224122346484
2.16-2.330.2551875.10.2353493X-RAY DIFFRACTION0.0194136368089
2.33-2.560.2541804.70.233621X-RAY DIFFRACTION0.0194157380191.4
2.56-2.940.2291774.50.2233726X-RAY DIFFRACTION0.0174132390394.5
2.94-3.70.2112185.40.1913812X-RAY DIFFRACTION0.0144167403096.7
3.7-29.880.1531944.70.1513922X-RAY DIFFRACTION0.0114220411697.5
2.2-2.30.36545.20.399993NEUTRON DIFFRACTION0.0492437104743
2.3-2.420.373574.90.3761114NEUTRON DIFFRACTION0.0492449117147.8
2.42-2.570.387705.30.3341242NEUTRON DIFFRACTION0.0462487131252.8
2.57-2.770.387765.50.3331303NEUTRON DIFFRACTION0.0442458137956.1
2.77-3.050.291694.20.2761580NEUTRON DIFFRACTION0.0352470164966.8
3.05-3.490.24411860.2221857NEUTRON DIFFRACTION0.0222465197580.1
3.49-4.40.1571054.70.1542136NEUTRON DIFFRACTION0.0152484224190.2
4.4-29.90.181034.50.1662183NEUTRON DIFFRACTION0.0182527228690.5

+
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