[English] 日本語
Yorodumi
- PDB-3atw: Structure-Based Design, Synthesis, Evaluation of Peptide-mimetic ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3atw
TitleStructure-Based Design, Synthesis, Evaluation of Peptide-mimetic SARS 3CL Protease Inhibitors
Components
  • 3C-Like Proteinase
  • peptide ACE-THR-VAL-ALC-HIS-H
KeywordsHYDROLASE/HYDROLASE INHIBITOR / hydrase proteinase converting / designed inhibitor / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


Assembly of the SARS-CoV-1 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / Transcription of SARS-CoV-1 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / K48-linked deubiquitinase activity / Replication of the SARS-CoV-1 genome / host cell endoplasmic reticulum / K63-linked deubiquitinase activity / SARS-CoV-1 modulates host translation machinery / viral genome replication ...Assembly of the SARS-CoV-1 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / Transcription of SARS-CoV-1 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / K48-linked deubiquitinase activity / Replication of the SARS-CoV-1 genome / host cell endoplasmic reticulum / K63-linked deubiquitinase activity / SARS-CoV-1 modulates host translation machinery / viral genome replication / methyltransferase activity / SARS-CoV-1 activates/modulates innate immune responses / 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 / 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 / viral protein processing / host cell perinuclear region of cytoplasm / lyase activity / 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 / RNA-directed RNA polymerase activity / proteolysis / zinc ion binding / identical protein binding / membrane
Similarity search - Function
Non-structural protein 3, SUD-N macrodomain, SARS-CoV / main proteinase (3clpro) structure, domain 3 / main proteinase (3clpro) structure, domain 3 / 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 ...Non-structural protein 3, SUD-N macrodomain, SARS-CoV / main proteinase (3clpro) structure, domain 3 / main proteinase (3clpro) structure, domain 3 / 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 / Trypsin-like serine proteases / 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 / Thrombin, subunit H / 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 / Beta Barrel / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
peptide ACE-THR-VAL-ALC-HIS-H / Replicase polyprotein 1a
Similarity search - Component
Biological speciesSARS coronavirus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.36 Å
AuthorsAkaji, K. / Konno, H. / Mitsui, H. / Teruya, K. / Hattori, Y. / Ozaki, T. / Kusunoki, M. / Sanjho, A.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors.
Authors: Akaji, K. / Konno, H. / Mitsui, H. / Teruya, K. / Shimamoto, Y. / Hattori, Y. / Ozaki, T. / Kusunoki, M. / Sanjoh, A.
History
DepositionJan 20, 2011Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 14, 2011Provider: repository / Type: Initial release
Revision 1.1Dec 12, 2012Group: Other
Revision 1.2Jul 1, 2015Group: Structure summary
Revision 1.3Nov 1, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_value_order / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details
Revision 1.4Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3C-Like Proteinase
B: 3C-Like Proteinase
C: peptide ACE-THR-VAL-ALC-HIS-H
D: peptide ACE-THR-VAL-ALC-HIS-H


Theoretical massNumber of molelcules
Total (without water)68,7054
Polymers68,7054
Non-polymers00
Water4,486249
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4990 Å2
ΔGint-24 kcal/mol
Surface area25260 Å2
MethodPISA
Unit cell
Length a, b, c (Å)54.517, 58.546, 67.745
Angle α, β, γ (deg.)94.29, 104.03, 106.64
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein 3C-Like Proteinase / 3CL-PRO / 3CLp / nsp5


Mass: 33832.602 Da / Num. of mol.: 2 / Mutation: R188I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) SARS coronavirus / Gene: 1a / Plasmid: pMAL-3CL-R188I / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: P0C6U8, SARS coronavirus main proteinase
#2: Protein/peptide peptide ACE-THR-VAL-ALC-HIS-H


Type: Peptide-like / Class: Enzyme inhibitor / Mass: 519.657 Da / Num. of mol.: 2 / Source method: obtained synthetically
Details: The peptide was designed and chemically synthesized.
References: peptide ACE-THR-VAL-ALC-HIS-H
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 249 / 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: 2.89 Å3/Da / Density % sol: 57.44 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 9-11%(w/v) of PEG 20000, 100mM MES pH 6.0, 5mM DTT, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 95 K
Diffraction sourceSource: SYNCHROTRON / Site: Photon Factory / Beamline: BL-6A / Wavelength: 0.978 Å
DetectorType: ADSC QUANTUM 4r / Detector: CCD / Date: May 23, 2009
RadiationMonochromator: Triangular with an asymmetric angle of 7.8 A / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. all: 31735 / Num. obs: 31735 / % possible obs: 96.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 2 % / Rmerge(I) obs: 0.079 / Rsym value: 0.079 / Net I/σ(I): 11.8
Reflection shellResolution: 2.36→2.4 Å / Rmerge(I) obs: 0.232 / Mean I/σ(I) obs: 3.8 / Num. unique all: 2409 / % possible all: 77.8

-
Processing

Software
NameVersionClassification
HKL-2000data collection
MOLREPphasing
REFMAC5.5.0088refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2ZU5

2zu5


Resolution: 2.36→46.4 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.906 / SU B: 7.049 / SU ML: 0.171 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.242 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.24335 1570 5.1 %RANDOM
Rwork0.20091 ---
obs0.20309 29416 97 %-
all-29416 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 33.738 Å2
Baniso -1Baniso -2Baniso -3
1--2.42 Å2-0.29 Å21.04 Å2
2--2.69 Å2-0.04 Å2
3---0.06 Å2
Refinement stepCycle: LAST / Resolution: 2.36→46.4 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4722 0 0 249 4971
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0224828
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.3081.966560
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5235598
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.96724.434212
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.92115770
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.2781522
X-RAY DIFFRACTIONr_chiral_restr0.0750.2746
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0213664
X-RAY DIFFRACTIONr_gen_planes_other
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_it0.5161.52984
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.97824826
X-RAY DIFFRACTIONr_scbond_it1.23831844
X-RAY DIFFRACTIONr_scangle_it2.034.51734
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.353→2.414 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.298 92 -
Rwork0.231 1736 -
obs--77.2 %

+
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