[English] 日本語
Yorodumi
- PDB-5n5o: Structure of SARS coronavirus main protease in complex with the a... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5n5o
TitleStructure of SARS coronavirus main protease in complex with the alpha-ketoamide (S)-N-benzyl-3-((S)-2-cinnamamido-3-cyclopropylpropanamido)-2-oxo-4-((S)-2-oxopyrrolidin-3-yl)butanamide (Cinnamoyl-cyclopropylalanine-GlnLactam-CO-CO-NH-benzyl)
ComponentsReplicase polyprotein 1ab
KeywordsHYDROLASE / Viral protease / coronavirus / alpha-ketoamide / inhibitor
Function / homology
Function and homology information


positive regulation of ubiquitin-specific protease activity / Maturation of replicase proteins / Assembly of the SARS-CoV-1 Replication-Transcription Complex (RTC) / Transcription of SARS-CoV-1 sgRNAs / Lys48-specific deubiquitinase activity / Translation of Replicase and Assembly of the Replication Transcription Complex / Replication of the SARS-CoV-1 genome / mRNA (guanine-N7-)-methyltransferase activity / Transferases; Transferring one-carbon groups; Methyltransferases / viral RNA-directed RNA polymerase complex ...positive regulation of ubiquitin-specific protease activity / Maturation of replicase proteins / Assembly of the SARS-CoV-1 Replication-Transcription Complex (RTC) / Transcription of SARS-CoV-1 sgRNAs / Lys48-specific deubiquitinase activity / Translation of Replicase and Assembly of the Replication Transcription Complex / Replication of the SARS-CoV-1 genome / mRNA (guanine-N7-)-methyltransferase activity / Transferases; Transferring one-carbon groups; Methyltransferases / viral RNA-directed RNA polymerase complex / exoribonuclease complex / viral replication complex formation and maintenance / endopeptidase complex / endoribonuclease complex / 5'-3' RNA helicase activity / mRNA cap methyltransferase complex / RNA phosphodiester bond hydrolysis, exonucleolytic / positive regulation of RNA biosynthetic process / Lyases; Phosphorus-oxygen lyases / mRNA methylation / double membrane vesicle viral factory outer membrane / suppression by virus of host translation / ISG15-specific peptidase activity / SARS coronavirus main proteinase / suppression by virus of host type I interferon production / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / 3'-5'-exoribonuclease activity / host cell endosome / host cell endoplasmic reticulum-Golgi intermediate compartment / induction by virus of catabolism of host mRNA / cytoplasmic viral factory / protein K48-linked deubiquitination / G-quadruplex RNA binding / suppression by virus of host ISG15-protein conjugation / 7-methylguanosine mRNA capping / RNA-templated transcription / viral transcription / suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / suppression by virus of host toll-like receptor signaling pathway / host cell endoplasmic reticulum / host cell Golgi apparatus / suppression by virus of host NF-kappaB cascade / modulation by virus of host protein ubiquitination / protein K63-linked deubiquitination / methyltransferase cap1 / positive stranded viral RNA replication / mRNA (nucleoside-2'-O-)-methyltransferase activity / double-stranded RNA binding / positive regulation of viral genome replication / suppression by virus of host TRAF activity / protein autoprocessing / helicase activity / ubiquitinyl hydrolase 1 / DNA helicase / cysteine-type deubiquitinase activity / DNA helicase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / protein processing / host cell perinuclear region of cytoplasm / viral protein processing / integral to membrane of host cell / RNA helicase / lyase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / suppression by virus of host gene expression / endonuclease activity / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed 5'-3' RNA polymerase activity / DNA-templated transcription / host cell cytoplasm / protein dimerization activity / suppression by virus of host type I interferon-mediated signaling pathway / ATP hydrolysis activity / zinc ion binding / integral component of membrane / ATP binding / identical protein binding
Similarity search - Function
Non-structural protein 3, SUD-N macrodomain, SARS-CoV / main proteinase (3clpro) structure, domain 3 / main proteinase (3clpro) structure, domain 3 / RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Nonstructural protein 14, betacoronavirus ...Non-structural protein 3, SUD-N macrodomain, SARS-CoV / main proteinase (3clpro) structure, domain 3 / main proteinase (3clpro) structure, domain 3 / RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Nonstructural protein 14, betacoronavirus / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) domain profile. / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / Viral (Superfamily 1) RNA helicase / NSP15, NendoU domain, coronavirus / Nonstructural protein 13, 1B domain, coronavirus / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nonstructural protein 15, middle domain, coronavirus / Non-structural protein NSP16, coronavirus-like / Non-structural protein NSP15, N-terminal domain superfamily, coronavirus / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Coronavirus replicase NSP15, N-terminal oligomerization / Non-structural protein 14, coronavirus / Non-structural protein NSP15, middle domain superfamily / RNA polymerase, N-terminal, coronavirus / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / NendoU domain, nidovirus / Endoribonuclease EndoU-like / Non-structural protein NSP3, SUD-N (Mac2) domain, betacoronavirus / Sarbecovirus Nsp3c-N domain profile. / NSP1 globular domain superfamily, betacoronavirus / Polyprotein cleavage domain PL2pro superfamily, betacoronavirus / Betacoronavirus replicase NSP3, N-terminal / Non-structural protein 2, SARS-CoV-like / Non-structural protein NSP3, N-terminal, betacoronavirus / Betacoronavirus SUD-C domain / Non-structural protein NSP3, SUD-N (Mac2) domain superfamily, betacoronavirus / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / : / Betacoronavirus (BetaCoV) Nsp1 C-terminal domain profile. / : / : / : / Coronavirus (CoV) Nsp1 globular domain profile. / Betacoronavirus Nsp3c-M domain profile. / : / Non-structural protein NSP3, SUD-M domain, betacoronavirus / NSP1, globular domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus / Betacoronavirus replicase NSP1 / Betacoronavirus single-stranded poly(A) binding domain / Coronavirus (CoV) ExoN/MTase coactivator domain profile. / Coronavirus Nsp9 single-stranded RNA (ssRNA)-binding domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp8 cofactor domain profile. / Coronavirus RNA-dependent RNA polymerase (RdRp) Nsp7 cofactor domain profile. / Betacoronavirus Nsp3e nucleic acid-binding (NAB) domain profile. / Betacoronavirus Nsp3c-C 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 NSP3A domain-like superfamily / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Papain-like protease, N-terminal domain superfamily, coronavirus / Papain-like viral protease, palm and finger domains, coronavirus / Nonstructural protein 2, N-terminal domain, coronavirus / Coronavirus replicase NSP2, N-terminal / Non-structural protein 2, C-terminal domain, coronavirus / Coronavirus replicase NSP2, C-terminal / Coronavirus Nsp3d Ubl domain profile. / Coronavirus Nsp3a Ubl domain profile. / NSP3, first ubiquitin-like (Ubl) domain, coronavirus / NSP3, second ubiquitin-like (Ubl) domain, coronavirus / Coronavirus Nsp4 C-terminal (Nsp4C) domain profile. / Papain-like protease, thumb domain superfamily, coronavirus / Non-structural protein NSP7, coronavirus / Coronavirus replicase NSP7 / Peptidase family C16 domain profile. / Coronavirus endopeptidase C30 / RNA synthesis protein NSP10 superfamily, coronavirus / Coronavirus replicase NSP8 / Coronavirus RNA synthesis protein NSP10 / Non-structural protein NSP4, N-terminal, coronavirus / Coronavirus replicase NSP6 / Coronavirus replicase NSP4, N-terminal / Coronavirus replicase NSP3, C-terminal / Coronavirus main protease (M-pro) domain profile. / Coronavirus replicase NSP4, C-terminal / Coronavirus papain-like peptidase / Coronavirus replicase NSP3, C-terminal / Non-structural protein NSP9 superfamily, coronavirus
Similarity search - Domain/homology
Chem-8O5 / Replicase polyprotein 1ab
Similarity search - Component
Biological speciesSARS coronavirus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsZhang, L. / Hilgenfeld, R.
Funding support Germany, 1items
OrganizationGrant numberCountry
German Center for Infection ResearchTTU 01.803 Germany
CitationJournal: To Be Published
Title: Alpha-ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication
Authors: Lin, D. / Zhang, L. / Kusov, Y. / Nian, Y. / Ma, Q. / Wang, J. / Leyssen, P. / Lanko, K. / Neyts, J. / de Wilde, A. / Snijder, E.J. / Liu, H. / Hilgenfeld, R.
History
DepositionFeb 14, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 7, 2018Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Replicase polyprotein 1ab
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4092
Polymers33,8771
Non-polymers5331
Water3,855214
1
A: Replicase polyprotein 1ab
hetero molecules

A: Replicase polyprotein 1ab
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,8194
Polymers67,7532
Non-polymers1,0652
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Buried area2470 Å2
ΔGint-8 kcal/mol
Surface area26700 Å2
MethodPISA
Unit cell
Length a, b, c (Å)109.165, 81.873, 53.499
Angle α, β, γ (deg.)90.00, 104.34, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-704-

HOH

-
Components

#1: Protein Replicase polyprotein 1ab / pp1ab / ORF1ab polyprotein


Mass: 33876.637 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) SARS coronavirus / Gene: rep, 1a-1b / Production host: Escherichia coli (E. coli)
References: UniProt: P0C6X7, ubiquitinyl hydrolase 1, SARS coronavirus main proteinase, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases, RNA-directed RNA polymerase, DNA ...References: UniProt: P0C6X7, ubiquitinyl hydrolase 1, SARS coronavirus main proteinase, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases, RNA-directed RNA polymerase, DNA helicase, RNA helicase, Transferases; Transferring one-carbon groups; Methyltransferases, Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters, Hydrolases; Acting on ester bonds
#2: Chemical ChemComp-8O5 / (2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide


Mass: 532.631 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C30H36N4O5
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 214 / 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: 3.42 Å3/Da / Density % sol: 64.02 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 6 - 8% polyethylene glycol 6000, 0.1 M MES, pH 6.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, DESY / Beamline: P11 / Wavelength: 0.9919 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 25, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9919 Å / Relative weight: 1
ReflectionResolution: 2→43.83 Å / Num. obs: 30329 / % possible obs: 98.3 % / Redundancy: 3.3 % / CC1/2: 0.997 / Rmerge(I) obs: 0.06 / Rpim(I) all: 0.039 / Net I/σ(I): 10.5
Reflection shellResolution: 2→2.11 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.507 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 4358 / CC1/2: 0.804 / Rpim(I) all: 0.331 / % possible all: 97.4

-
Processing

Software
NameVersionClassification
REFMAC5.8.0158refinement
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: SARS-CoV main protease

Resolution: 2→43.83 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.937 / SU B: 4.888 / SU ML: 0.128 / Cross valid method: THROUGHOUT / ESU R: 0.149 / ESU R Free: 0.155 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25152 1501 5 %RANDOM
Rwork0.19222 ---
obs0.19512 28787 98.07 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 44.062 Å2
Baniso -1Baniso -2Baniso -3
1--2.71 Å20 Å21.59 Å2
2--1.34 Å20 Å2
3---0.49 Å2
Refinement stepCycle: 1 / Resolution: 2→43.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2371 0 39 214 2624
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0180.0192467
X-RAY DIFFRACTIONr_bond_other_d0.0020.022219
X-RAY DIFFRACTIONr_angle_refined_deg1.9081.9653351
X-RAY DIFFRACTIONr_angle_other_deg1.19735155
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.3455307
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.72424.352108
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.13815393
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.8621512
X-RAY DIFFRACTIONr_chiral_restr0.1370.2378
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0212778
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02518
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.9744.2161228
X-RAY DIFFRACTIONr_mcbond_other3.974.2151227
X-RAY DIFFRACTIONr_mcangle_it5.1426.3021535
X-RAY DIFFRACTIONr_mcangle_other5.1416.3031536
X-RAY DIFFRACTIONr_scbond_it4.6254.6441239
X-RAY DIFFRACTIONr_scbond_other4.6234.6451240
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.6356.7911814
X-RAY DIFFRACTIONr_long_range_B_refined8.07250.3762677
X-RAY DIFFRACTIONr_long_range_B_other8.07150.3712678
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2→2.052 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.369 114 -
Rwork0.296 2138 -
obs--98.3 %

+
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