[English] 日本語
Yorodumi
- EMDB-10220: Cryo-EM structure of rhinovirus-B5 complexed to antiviral OBR-5-340 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-10220
TitleCryo-EM structure of rhinovirus-B5 complexed to antiviral OBR-5-340
Map dataNone
Sample
  • Virus: Human rhinovirus B5
    • Protein or peptide: Rhinovirus B5 VP4
    • Protein or peptide: Rhinovirus B5 VP2
    • Protein or peptide: Rhinovirus B5 VP1
    • Protein or peptide: Rhinovirus B5 VP3
  • Ligand: 6-phenyl-~{N}3-[4-(trifluoromethyl)phenyl]-1~{H}-pyrazolo[3,4-d]pyrimidine-3,4-diamine
Function / homology
Function and homology information


RNA-protein covalent cross-linking / : / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane ...RNA-protein covalent cross-linking / : / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / viral capsid / : / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / host cell cytoplasm / RNA helicase activity / induction by virus of host autophagy / symbiont entry into host cell / RNA-directed RNA polymerase / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / proteolysis / RNA binding / ATP binding / metal ion binding / cytoplasm
Similarity search - Function
Picornavirus coat protein VP4 superfamily / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) ...Picornavirus coat protein VP4 superfamily / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein / VP4
Similarity search - Component
Biological speciesHuman rhinovirus B5
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsWald J / Goessweiner-Mohr N / Blaas D / Pasin M
CitationJournal: Proc Natl Acad Sci U S A / Year: 2019
Title: Cryo-EM structure of pleconaril-resistant rhinovirus-B5 complexed to the antiviral OBR-5-340 reveals unexpected binding site.
Authors: Jiri Wald / Marion Pasin / Martina Richter / Christin Walther / Neann Mathai / Johannes Kirchmair / Vadim A Makarov / Nikolaus Goessweiner-Mohr / Thomas C Marlovits / Irene Zanella / Antonio ...Authors: Jiri Wald / Marion Pasin / Martina Richter / Christin Walther / Neann Mathai / Johannes Kirchmair / Vadim A Makarov / Nikolaus Goessweiner-Mohr / Thomas C Marlovits / Irene Zanella / Antonio Real-Hohn / Nuria Verdaguer / Dieter Blaas / Michaela Schmidtke /
Abstract: Viral inhibitors, such as pleconaril and vapendavir, target conserved regions in the capsids of rhinoviruses (RVs) and enteroviruses (EVs) by binding to a hydrophobic pocket in viral capsid protein 1 ...Viral inhibitors, such as pleconaril and vapendavir, target conserved regions in the capsids of rhinoviruses (RVs) and enteroviruses (EVs) by binding to a hydrophobic pocket in viral capsid protein 1 (VP1). In resistant RVs and EVs, bulky residues in this pocket prevent their binding. However, recently developed pyrazolopyrimidines inhibit pleconaril-resistant RVs and EVs, and computational modeling has suggested that they also bind to the hydrophobic pocket in VP1. We studied the mechanism of inhibition of pleconaril-resistant RVs using RV-B5 (1 of the 7 naturally pleconaril-resistant rhinoviruses) and OBR-5-340, a bioavailable pyrazolopyrimidine with proven in vivo activity, and determined the 3D-structure of the protein-ligand complex to 3.6 Å with cryoelectron microscopy. Our data indicate that, similar to other capsid binders, OBR-5-340 induces thermostability and inhibits viral adsorption and uncoating. However, we found that OBR-5-340 attaches closer to the entrance of the pocket than most other capsid binders, whose viral complexes have been studied so far, showing only marginal overlaps of the attachment sites. Comparing the experimentally determined 3D structure with the control, RV-B5 incubated with solvent only and determined to 3.2 Å, revealed no gross conformational changes upon OBR-5-340 binding. The pocket of the naturally OBR-5-340-resistant RV-A89 likewise incubated with OBR-5-340 and solved to 2.9 Å was empty. Pyrazolopyrimidines have a rigid molecular scaffold and may thus be less affected by a loss of entropy upon binding. They interact with less-conserved regions than known capsid binders. Overall, pyrazolopyrimidines could be more suitable for the development of new, broadly active inhibitors.
History
DepositionAug 14, 2019-
Header (metadata) releaseAug 28, 2019-
Map releaseSep 4, 2019-
UpdateDec 2, 2020-
Current statusDec 2, 2020Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6sk5
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6sk5
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_10220.png

Downloads & links

-
Map

FileDownload / File: emd_10220.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationNone
Voxel sizeX=Y=Z: 0.97 Å
Density
Contour LevelBy AUTHOR: 0.0478 / Movie #1: 0.01
Minimum - Maximum-0.051457036 - 0.0767982
Average (Standard dev.)0.00050779484 (±0.004734414)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-224-224-224
Dimensions450450450
Spacing450450450
CellA=B=C: 436.5 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.970.970.97
M x/y/z450450450
origin x/y/z0.0000.0000.000
length x/y/z436.500436.500436.500
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS-224-224-224
NC/NR/NS450450450
D min/max/mean-0.0510.0770.001

-
Supplemental data

-
Mask #1

Fileemd_10220_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_10220_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_10220_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human rhinovirus B5

EntireName: Human rhinovirus B5
Components
  • Virus: Human rhinovirus B5
    • Protein or peptide: Rhinovirus B5 VP4
    • Protein or peptide: Rhinovirus B5 VP2
    • Protein or peptide: Rhinovirus B5 VP1
    • Protein or peptide: Rhinovirus B5 VP3
  • Ligand: 6-phenyl-~{N}3-[4-(trifluoromethyl)phenyl]-1~{H}-pyrazolo[3,4-d]pyrimidine-3,4-diamine

-
Supramolecule #1: Human rhinovirus B5

SupramoleculeName: Human rhinovirus B5 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 / NCBI-ID: 147714 / Sci species name: Human rhinovirus B5 / Sci species strain: B5 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No
Host (natural)Organism: Homo sapiens (human)
Virus shellShell ID: 1 / Name: VP1-4 / Diameter: 302.0 Å

-
Macromolecule #1: Rhinovirus B5 VP4

MacromoleculeName: Rhinovirus B5 VP4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human rhinovirus B5
Molecular weightTheoretical: 7.335049 KDa
SequenceString:
MGAQVSTQKS GSHENQNILT NGSNQTFTVI NYYKDAASSS SAGQSFSMDP SKFTEPVKDI MLKGAPALN

-
Macromolecule #2: Rhinovirus B5 VP2

MacromoleculeName: Rhinovirus B5 VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Human rhinovirus B5
Molecular weightTheoretical: 27.507256 KDa
SequenceString: GYSDRVEQIT LGNSTITTQE AANSIVAYGE WPSFLSDVDA SDVNKTTKPD TSACRFYTLD SKMWTQGSKG WCWKLPDALK DMGIFGQNM FFHSQGRTGY TIHVQCNATK FHSGCLLVVV IPEHQLASAE GGNVSVLYDK THPGEKGIDL SEADSTGPMK D PLYMMDGT ...String:
GYSDRVEQIT LGNSTITTQE AANSIVAYGE WPSFLSDVDA SDVNKTTKPD TSACRFYTLD SKMWTQGSKG WCWKLPDALK DMGIFGQNM FFHSQGRTGY TIHVQCNATK FHSGCLLVVV IPEHQLASAE GGNVSVLYDK THPGEKGIDL SEADSTGPMK D PLYMMDGT LIGNSLIFPH QFINLRTNNT ATIVVPYINS VPMDSMTRHN NLSLMVIPIV DITATSGTTP SIPVTITIAP MF LELSGIR SKAVI

-
Macromolecule #3: Rhinovirus B5 VP1

MacromoleculeName: Rhinovirus B5 VP1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human rhinovirus B5
Molecular weightTheoretical: 32.743861 KDa
SequenceString: GLEDDLVEVI VDKAQQTLAS IKSDSKHTQK VPSLTANETG ATLPTTPSDS VETRTTLMHY TGSETTLENF LGRAACVHVV EIVNKRPTD TEEHRMQLLF NNWKINLSSL VQLRRKLEMF TYVRFDSEYT IIATSSQPNE AKFSSNLTIQ AMFIPPGAPN P KKWDDYTW ...String:
GLEDDLVEVI VDKAQQTLAS IKSDSKHTQK VPSLTANETG ATLPTTPSDS VETRTTLMHY TGSETTLENF LGRAACVHVV EIVNKRPTD TEEHRMQLLF NNWKINLSSL VQLRRKLEMF TYVRFDSEYT IIATSSQPNE AKFSSNLTIQ AMFIPPGAPN P KKWDDYTW QSATNPSVFF NVGKSARFSV PYLGIASAYN CFYDGYSHDN STTPYGINVL NHMGSMAFRV VNEHDNHTTH VK VRVYHRA KHIRAWVPRA PRALEYLHIG RTNYKQSPQN PIKTRKTIST Y

-
Macromolecule #4: Rhinovirus B5 VP3

MacromoleculeName: Rhinovirus B5 VP3 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Human rhinovirus B5
Molecular weightTheoretical: 25.500168 KDa
SequenceString: GLPTVLTPGS EQFLTTDDRQ SPSAMPNYEP TPLIHIPGEV KNLLEIAQVD TLIPLNNTTN TTGLGMYRIP LVQNMQGEQV FGFRLYLGD GVLKTTLLGE LCQYFTHWAG SLRLSFMYTG PALSSAKLLI AYTPPGAQGP TKRKEAMLGT HVVWDIGLQS T VVLNIPWT ...String:
GLPTVLTPGS EQFLTTDDRQ SPSAMPNYEP TPLIHIPGEV KNLLEIAQVD TLIPLNNTTN TTGLGMYRIP LVQNMQGEQV FGFRLYLGD GVLKTTLLGE LCQYFTHWAG SLRLSFMYTG PALSSAKLLI AYTPPGAQGP TKRKEAMLGT HVVWDIGLQS T VVLNIPWT SGVQYRYTDP DTYTSAGFVS CWYQTSLVLP PQTQQTVYML GFISACPDFK LRLMKDTQSI HQ

-
Macromolecule #5: 6-phenyl-~{N}3-[4-(trifluoromethyl)phenyl]-1~{H}-pyrazolo[3,4-d]p...

MacromoleculeName: 6-phenyl-~{N}3-[4-(trifluoromethyl)phenyl]-1~{H}-pyrazolo[3,4-d]pyrimidine-3,4-diamine
type: ligand / ID: 5 / Number of copies: 1 / Formula: LGQ
Molecular weightTheoretical: 370.331 Da
Chemical component information

ChemComp-LGQ:
6-phenyl-~{N}3-[4-(trifluoromethyl)phenyl]-1~{H}-pyrazolo[3,4-d]pyrimidine-3,4-diamine

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4 / Component:
NameConcentration
PBS
DMSODimethyl sulfoxide10.0 %
GridModel: Homemade / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 0.4 nm / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK III

-
Electron microscopy

MicroscopeFEI POLARA 300
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-25 / Number real images: 2547 / Average exposure time: 5.0 sec. / Average electron dose: 40.0 e/Å2
Experimental equipment
Model: Tecnai Polara / Image courtesy: FEI Company

-
Image processing

CTF correctionSoftware - Name: CTFFIND (ver. 4.1)
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C60 (60 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 46070

-
Atomic model buiding 1

Initial modelPDB ID:

1aym

DetailsRosetta: DiMaio, F. et al. Atomic-accuracy models from 4.5-A cryo-electron microscopy data with density-guided iterative local refinement. Nat. Meth (2015). doi:10.1038/nmeth.3286
RefinementSpace: REAL
Output model

PDB-6sk5:
Cryo-EM structure of rhinovirus-B5 complexed to antiviral OBR-5-340

+
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