[English] 日本語
Yorodumi
- PDB-6vkc: Crystal Structure of Inhibitor JNJ-36811054 in Complex with Prefu... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vkc
TitleCrystal Structure of Inhibitor JNJ-36811054 in Complex with Prefusion RSV F Glycoprotein
ComponentsPrefusion RSV F (DS-Cav1),Envelope glycoprotein
KeywordsVIRAL PROTEIN / Inhibitor / complex
Function / homology
Function and homology information


symbiont-mediated induction of syncytium formation / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / Maturation of hRSV A proteins / Assembly and release of respiratory syncytial virus (RSV) virions / Respiratory syncytial virus (RSV) attachment and entry / host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / viral envelope ...symbiont-mediated induction of syncytium formation / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / Maturation of hRSV A proteins / Assembly and release of respiratory syncytial virus (RSV) virions / Respiratory syncytial virus (RSV) attachment and entry / host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / Fibritin C-terminal / Fibritin C-terminal region
Similarity search - Domain/homology
Chem-R0J / D(-)-TARTARIC ACID / Envelope glycoprotein / Fusion glycoprotein F0 / Fusion glycoprotein F0
Similarity search - Component
Biological speciesHuman respiratory syncytial virus
Human immunodeficiency virus 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsMcLellan, J.S.
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (JNJ-53718678), a Potent and Orally ...Title: Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus.
Authors: Vendeville, S. / Tahri, A. / Hu, L. / Demin, S. / Cooymans, L. / Vos, A. / Kwanten, L. / Van den Berg, J. / Battles, M.B. / McLellan, J.S. / Koul, A. / Raboisson, P. / Roymans, D. / Jonckers, T.H.M.
History
DepositionJan 20, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 27, 2020Provider: repository / Type: Initial release
Revision 1.1Jul 1, 2020Group: Database references / Category: citation / citation_author
Item: _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_struct_special_symmetry / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.auth_asym_id / _atom_site.auth_seq_id ..._atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _chem_comp.name / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_special_symmetry.label_asym_id / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Aug 26, 2020Group: Database references / Derived calculations / Structure summary
Category: chem_comp / citation / struct_conn
Item: _chem_comp.pdbx_synonyms / _citation.journal_volume ..._chem_comp.pdbx_synonyms / _citation.journal_volume / _citation.page_first / _citation.page_last / _struct_conn.pdbx_leaving_atom_flag
Revision 2.2Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.3Oct 30, 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
F: Prefusion RSV F (DS-Cav1),Envelope glycoprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,79811
Polymers63,2181
Non-polymers1,58010
Water1,63991
1
F: Prefusion RSV F (DS-Cav1),Envelope glycoprotein
hetero molecules

F: Prefusion RSV F (DS-Cav1),Envelope glycoprotein
hetero molecules

F: Prefusion RSV F (DS-Cav1),Envelope glycoprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)194,39533
Polymers189,6553
Non-polymers4,74030
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Buried area20090 Å2
ΔGint-263 kcal/mol
Surface area48030 Å2
MethodPISA
Unit cell
Length a, b, c (Å)168.040, 168.040, 168.040
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number213
Space group name H-MP4132
Components on special symmetry positions
IDModelComponents
11F-609-

SO4

21F-609-

SO4

31F-786-

HOH

-
Components

-
Protein / Sugars , 2 types, 2 molecules F

#1: Protein Prefusion RSV F (DS-Cav1),Envelope glycoprotein


Mass: 63218.344 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human respiratory syncytial virus, (gene. exp.) Human immunodeficiency virus 1
Production host: Homo sapiens (human)
References: UniProt: Q84850, UniProt: M1E1E4, UniProt: P03420*PLUS
#2: Polysaccharide alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
LFucpa1-6DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-2/a6-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE

-
Non-polymers , 5 types, 100 molecules

#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-R0J / 3-{[5-chloro-1-(4,4,4-trifluorobutyl)-1H-imidazo[4,5-b]pyridin-2-yl]methyl}-1-cyclopropyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one


Mass: 450.845 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H18ClF3N6O / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-TAR / D(-)-TARTARIC ACID


Mass: 150.087 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H6O6
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 91 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.13 Å3/Da / Density % sol: 60.67 %
Crystal growTemperature: 293 K / Method: vapor diffusion / Details: 1.52M K/Na tartrate, 0.2M LiSO4, 0.1M CHES pH 9.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97926 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 20, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97926 Å / Relative weight: 1
ReflectionResolution: 2.6→46.61 Å / Num. obs: 25576 / % possible obs: 100 % / Redundancy: 20.1 % / Biso Wilson estimate: 54.74 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.178 / Rpim(I) all: 0.04 / Rrim(I) all: 0.182 / Net I/σ(I): 14.9 / Num. measured all: 514782 / Scaling rejects: 60
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.6-2.72211.7926397630500.5880.3991.8362.1100
9.01-46.6116.40.036120457330.9990.0090.03744.899.4

-
Processing

Software
NameVersionClassification
Aimless0.5.27data scaling
PHENIX1.13refinement
PDB_EXTRACT3.25data extraction
iMOSFLMdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5EA4

5ea4


Resolution: 2.6→46.606 Å / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 21.99
RfactorNum. reflection% reflection
Rfree0.2293 1280 5.02 %
Rwork0.1916 --
obs0.1934 25515 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 146.77 Å2 / Biso mean: 61.1089 Å2 / Biso min: 26.7 Å2
Refinement stepCycle: final / Resolution: 2.6→46.606 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3379 0 96 91 3566
Biso mean--109.29 48.5 -
Num. residues----437
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork
2.6004-2.70450.33451400.29312631
2.7045-2.82750.29911650.27552609
2.8275-2.97660.29671500.25072614
2.9766-3.1630.27111360.2272664
3.163-3.40720.20991380.20792660
3.4072-3.74990.26631300.1792687
3.7499-4.29220.20961270.16612715
4.2922-5.40640.17761460.1482737
5.4064-46.6060.21871480.18812918
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)
11.33-0.1469-0.52582.89171.33973.216-0.1292-0.0218-0.3850.23760.05370.05040.5929-0.1730.18790.2574-0.0216-0.00730.35650.07410.42063.1792-4.83318.6072
23.25872.90093.30265.41345.82747.095-0.47250.8246-0.2973-0.78320.4750.1592-0.61340.6522-0.1230.6198-0.04730.00270.51360.03840.51198.8556-9.4555-5.4228
31.54550.37270.16122.03661.50253.68840.00660.0956-0.6182-0.0974-0.05360.1860.8393-0.24760.00160.5001-0.0451-0.070.32810.00920.55654.9292-14.07716.345
40.3843-0.4595-0.45598.4366-0.54872.062-0.0569-0.1309-0.00210.12460.06530.08150.1352-0.12190.00830.2390.0146-0.00790.40690.04920.343910.45037.649830.0438
53.8179-0.04010.30615.3785-0.57433.27920.0829-0.37740.06460.1513-0.09650.55830.0843-0.3434-0.00440.290.07430.04290.4412-0.02990.2964-8.085219.970628.4386
67.42780.1525-0.82876.1989-0.45025.42810.2206-0.63290.79740.2949-0.0622-0.862-0.54750.4046-0.07830.5186-0.0187-0.09550.4407-0.03370.426419.308325.740936.4728
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'F' and (resid 26 through 73 )F26 - 73
2X-RAY DIFFRACTION2chain 'F' and (resid 74 through 148 )F74 - 148
3X-RAY DIFFRACTION3chain 'F' and (resid 149 through 332 )F149 - 332
4X-RAY DIFFRACTION4chain 'F' and (resid 333 through 403 )F333 - 403
5X-RAY DIFFRACTION5chain 'F' and (resid 404 through 469 )F404 - 469
6X-RAY DIFFRACTION6chain 'F' and (resid 470 through 506 )F470 - 506

+
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