[English] 日本語
Yorodumi
- PDB-8h7k: SARS-CoV-2 Mpro Double Mutant (H41A and T21I) in complex with nsp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8h7k
TitleSARS-CoV-2 Mpro Double Mutant (H41A and T21I) in complex with nsp4/5 peptidyl substrate
Components
  • 3C-like proteinase nsp5
  • nsp4/5 peptidyl substrate
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Mutant
Function / homology
Function and homology information


viral genome replication / methyltransferase 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 / Replication of the SARS-CoV-2 genome / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase ...viral genome replication / methyltransferase 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 / Replication of the SARS-CoV-2 genome / double membrane vesicle viral factory outer membrane / SARS coronavirus main proteinase / endonuclease 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 cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / methylation / omega peptidase activity / SARS-CoV-2 modulates host translation machinery / host cell Golgi apparatus / symbiont-mediated perturbation of host ubiquitin-like protein modification / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase 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 / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated suppression of host gene expression / viral translational frameshifting / symbiont-mediated activation of host autophagy / cysteine-type endopeptidase activity / lipid binding / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / proteolysis / zinc ion binding / membrane
Similarity search - Function
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. ...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. / : / : / Coronavirus replicase NSP7 / Coronavirus 3Ecto 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. / Coronavirus (CoV) Nsp3 Y domain profile. / Coronavirus Nsp4 C-terminal (Nsp4C) domain profile. / Coronavirus main protease (M-pro) domain profile. / Peptidase C30, coronavirus / Peptidase C16, coronavirus / Non-structural protein NSP9, coronavirus / Non-structural protein NSP7, coronavirus / Non-structural protein NSP8, coronavirus / RNA synthesis protein NSP10, coronavirus / Non-structural protein NSP4, C-terminal, coronavirus / RNA synthesis protein NSP10 superfamily, coronavirus / Non-structural protein NSP9 superfamily, coronavirus / Non-structural protein NSP7 superfamily, coronavirus / Non-structural protein NSP8 superfamily, coronavirus / Non-structural protein NSP4, C-terminal superfamily, coronavirus / Papain-like protease, thumb domain superfamily, coronavirus / Peptidase C30, domain 3, coronavirus / Non-structural protein 6, coronavirus / Coronavirus replicase NSP3, C-terminal / Non-structural protein NSP4, N-terminal, coronavirus / Coronavirus endopeptidase C30 / Coronavirus papain-like peptidase / Coronavirus replicase NSP8 / Coronavirus RNA synthesis protein NSP10 / Coronavirus replicase NSP4, C-terminal / Coronavirus replicase NSP6 / Coronavirus replicase NSP4, N-terminal / Coronavirus replicase NSP3, C-terminal / Coronavirus replicase NSP9 / Non-structural protein 3, X-domain-like / Appr-1"-p processing enzyme / Macro domain / Macro domain profile. / Macro domain / Macro domain-like / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Replicase polyprotein 1a
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.45 Å
AuthorsLin, M. / Liu, X.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)92169109 China
CitationJournal: Nature / Year: 2023
Title: Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir.
Authors: Duan, Y. / Zhou, H. / Liu, X. / Iketani, S. / Lin, M. / Zhang, X. / Bian, Q. / Wang, H. / Sun, H. / Hong, S.J. / Culbertson, B. / Mohri, H. / Luck, M.I. / Zhu, Y. / Liu, X. / Lu, Y. / Yang, ...Authors: Duan, Y. / Zhou, H. / Liu, X. / Iketani, S. / Lin, M. / Zhang, X. / Bian, Q. / Wang, H. / Sun, H. / Hong, S.J. / Culbertson, B. / Mohri, H. / Luck, M.I. / Zhu, Y. / Liu, X. / Lu, Y. / Yang, X. / Yang, K. / Sabo, Y. / Chavez, A. / Goff, S.P. / Rao, Z. / Ho, D.D. / Yang, H.
History
DepositionOct 20, 2022Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Oct 11, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 25, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3C-like proteinase nsp5
B: nsp4/5 peptidyl substrate


Theoretical massNumber of molelcules
Total (without water)34,8372
Polymers34,8372
Non-polymers00
Water4,143230
1
A: 3C-like proteinase nsp5
B: nsp4/5 peptidyl substrate

A: 3C-like proteinase nsp5
B: nsp4/5 peptidyl substrate


Theoretical massNumber of molelcules
Total (without water)69,6734
Polymers69,6734
Non-polymers00
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Buried area5670 Å2
ΔGint-30 kcal/mol
Surface area25320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)97.668, 80.884, 51.647
Angle α, β, γ (deg.)90.000, 114.520, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-437-

HOH

21A-551-

HOH

31A-555-

HOH

41A-562-

HOH

51A-614-

HOH

61A-621-

HOH

-
Components

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


Mass: 33770.531 Da / Num. of mol.: 1 / Mutation: H41A/T21I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: Escherichia coli (E. coli)
References: UniProt: P0DTC1, SARS coronavirus main proteinase
#2: Protein/peptide nsp4/5 peptidyl substrate


Mass: 1066.189 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: chemical production metagenome (others)
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 230 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.66 Å3/Da / Density % sol: 53.83 %
Crystal growTemperature: 293 K / Method: evaporation
Details: 0.2% w/v Lidocaine hydrochloride monohydrate, 0.2% w/v Procaine hydrochloride, 0.2% w/v Proparacaine hydrochloride, 0.2% w/v tetracaine hydrochloride, 0.1 M Buffer System 2 pH 7.5 (sodium ...Details: 0.2% w/v Lidocaine hydrochloride monohydrate, 0.2% w/v Procaine hydrochloride, 0.2% w/v Proparacaine hydrochloride, 0.2% w/v tetracaine hydrochloride, 0.1 M Buffer System 2 pH 7.5 (sodium HEPES, MOPS acid), 20% v/v Glycerol, 10% w/v PEG 4,000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 0.97853 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 23, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97853 Å / Relative weight: 1
ReflectionResolution: 1.45→19.94 Å / Num. obs: 64519 / % possible obs: 99.7 % / Redundancy: 6.692 % / Biso Wilson estimate: 21.58 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.034 / Rrim(I) all: 0.037 / Χ2: 0.858 / Net I/σ(I): 24.02 / Num. measured all: 431767
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.45-1.546.5940.7492.386817810371103390.9040.81399.7
1.54-1.646.7560.4364.1165863976597490.9560.47399.8
1.64-1.776.5860.2357.3659804909690810.9850.25599.8
1.77-1.946.8830.12313.8957607838283690.9950.13499.8
1.94-2.176.5920.06325.6449948759375770.9980.06899.8
2.17-2.56.980.04140.0446827672967090.9990.04499.7
2.5-3.056.5550.02954.9537294571056890.9990.03299.6
3.05-4.266.6570.02272.79296034473444710.02499.4
4.26-19.946.5040.0279.1916643261725590.9990.02297.8

-
Processing

Software
NameVersionClassification
XSCALEdata scaling
PHENIX1.19.2_4158refinement
PDB_EXTRACT3.27data extraction
autoPROCdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7dvp

7dvp


Resolution: 1.45→19.94 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 20.33 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1838 1996 3.1 %
Rwork0.1681 62467 -
obs0.1686 64463 99.83 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 101.27 Å2 / Biso mean: 32.9251 Å2 / Biso min: 15.38 Å2
Refinement stepCycle: final / Resolution: 1.45→19.94 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2393 0 0 230 2623
Biso mean---41.05 -
Num. residues----312
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.45-1.490.31181420.28634431457399
1.49-1.530.30191420.24644414583100
1.53-1.570.23931430.224344394582100
1.57-1.620.23851430.193244644607100
1.62-1.680.2041410.184744404581100
1.68-1.750.17461420.177444514593100
1.75-1.830.1871420.177644524594100
1.83-1.920.2041420.171744734615100
1.92-2.040.19231420.169344484590100
2.04-2.20.19771420.168244514593100
2.2-2.420.22321440.172244814625100
2.42-2.770.19871430.179344704613100
2.77-3.490.16761430.170344884631100
3.49-19.940.14871450.143245384683100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.04680.79640.72991.39950.82013.34310.0604-0.00990.0511-0.03410.0018-0.1783-0.21870.1562-0.06580.2052-0.02860.02590.189-0.01470.22142.089410.647812.1815
22.53130.50290.54384.2288-0.35664.92290.0492-0.12560.18460.1978-0.0302-0.4648-0.4030.55660.00630.262-0.0825-0.03650.268-0.07820.27357.183615.285726.6595
30.9530.1224-0.32223.3889-0.30891.9635-0.02490.06320.0588-0.14410.07340.0027-0.1357-0.0118-0.0420.1718-0.01970.00430.17-0.01170.1424-2.42475.185711.1121
40.94610.48010.28881.10210.52962.21820.0438-0.0428-0.12350.09780.0333-0.1210.14620.1004-0.08690.1521-0.01060.00470.1845-0.00240.1988-3.8824-4.485815.8176
53.5319-0.12061.36832.58780.85422.87390.0072-0.3008-0.33120.18880.090.29070.4782-0.5853-0.08870.2621-0.11010.02740.28950.00270.2829-19.5614-18.37194.3714
65.6015-0.31070.08874.88670.35844.7952-0.01050.2138-0.4152-0.08320.0106-0.14890.3375-0.064-0.01470.1984-0.07060.00990.2155-0.04620.1608-11.9599-16.25770.4229
77.34813.7618-1.05497.1797-2.66818.2340.0877-0.37470.03390.37-0.0277-1.2134-0.21720.79310.03330.2077-0.0208-0.0210.37-0.03830.412813.43211.723621.0696
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 43 )A1 - 43
2X-RAY DIFFRACTION2chain 'A' and (resid 44 through 91 )A44 - 91
3X-RAY DIFFRACTION3chain 'A' and (resid 92 through 155 )A92 - 155
4X-RAY DIFFRACTION4chain 'A' and (resid 156 through 213 )A156 - 213
5X-RAY DIFFRACTION5chain 'A' and (resid 214 through 260 )A214 - 260
6X-RAY DIFFRACTION6chain 'A' and (resid 261 through 302 )A261 - 302
7X-RAY DIFFRACTION7chain 'B' and (resid 1 through 10 )B1 - 10

+
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