+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20766 | |||||||||
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Title | Structure of the EVA71 strain 11316 capsid | |||||||||
Map data | cryo EM map of the EVA71 strain 11316 capsid | |||||||||
Sample |
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Keywords | Enterovirus / VIRUS | |||||||||
Function / homology | Function and homology information symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / 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 / symbiont-mediated suppression of host gene expression ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / 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 / symbiont-mediated suppression of host gene expression / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | |||||||||
Biological species | Enterovirus A71 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.04 Å | |||||||||
Authors | Lee H / Hafenstein S | |||||||||
Citation | Journal: J Med Chem / Year: 2020 Title: Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors. Authors: Belén Martínez-Gualda / Liang Sun / Olaia Martí-Marí / Sam Noppen / Rana Abdelnabi / Carol M Bator / Ernesto Quesada / Leen Delang / Carmen Mirabelli / Hyunwook Lee / Dominique Schols / ...Authors: Belén Martínez-Gualda / Liang Sun / Olaia Martí-Marí / Sam Noppen / Rana Abdelnabi / Carol M Bator / Ernesto Quesada / Leen Delang / Carmen Mirabelli / Hyunwook Lee / Dominique Schols / Johan Neyts / Susan Hafenstein / María-José Camarasa / Federico Gago / Ana San-Félix / Abstract: Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection for which ...Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection for which no antiviral therapies are available. We describe here the discovery of potent entry dual inhibitors of HIV and EV71. These compounds contain in their structure three or four tryptophan (Trp) residues linked to a central scaffold. Critical for anti-HIV/EV71 activity is the presence of extra phenyl rings, bearing one or two carboxylates, at the C2 position of the indole ring of each Trp residue. The most potent derivatives, and , inhibit early steps of the replicative cycles of HIV-1 and EV-A71 by interacting with their respective viral surfaces (glycoprotein gp120 of HIV and the fivefold axis of the EV-A71 capsid). The high potency, low toxicity, facile chemical synthesis, and great opportunities for chemical optimization make them useful prototypes for future medicinal chemistry studies. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20766.map.gz | 218.7 MB | EMDB map data format | |
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Header (meta data) | emd-20766-v30.xml emd-20766.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
Images | emd_20766.png | 94.2 KB | ||
Filedesc metadata | emd-20766.cif.gz | 5.5 KB | ||
Others | emd_20766_additional.map.gz | 263.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20766 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20766 | HTTPS FTP |
-Validation report
Summary document | emd_20766_validation.pdf.gz | 519.8 KB | Display | EMDB validaton report |
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Full document | emd_20766_full_validation.pdf.gz | 519.4 KB | Display | |
Data in XML | emd_20766_validation.xml.gz | 7.6 KB | Display | |
Data in CIF | emd_20766_validation.cif.gz | 8.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20766 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20766 | HTTPS FTP |
-Related structure data
Related structure data | 6uh1MC 6uh6C 6uh7C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20766.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | cryo EM map of the EVA71 strain 11316 capsid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Sharpened map of the EVA71 strain 11316 capsid
File | emd_20766_additional.map | ||||||||||||
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Annotation | Sharpened map of the EVA71 strain 11316 capsid | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Enterovirus A71
Entire | Name: Enterovirus A71 |
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Components |
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-Supramolecule #1: Enterovirus A71
Supramolecule | Name: Enterovirus A71 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 / NCBI-ID: 39054 / Sci species name: Enterovirus A71 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No |
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-Macromolecule #1: VP1
Macromolecule | Name: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus A71 |
Molecular weight | Theoretical: 32.748754 KDa |
Sequence | String: GDRVADVIES SIGDSVSRAL TQALPAPTGQ NTQVSSHRLD TGEVPALQAA EIGASSNTSD ESMIETRCVL NSHSTAETTL DSFFSRAGL VGEIDLPLEG TTNPNGYANW DIDITGYAQM RRKVELFTYM RFDAEFTFVA CTPTGQVVPQ LLQYMFVPPG A PKPESRES ...String: GDRVADVIES SIGDSVSRAL TQALPAPTGQ NTQVSSHRLD TGEVPALQAA EIGASSNTSD ESMIETRCVL NSHSTAETTL DSFFSRAGL VGEIDLPLEG TTNPNGYANW DIDITGYAQM RRKVELFTYM RFDAEFTFVA CTPTGQVVPQ LLQYMFVPPG A PKPESRES LAWQTATNPS VFVKLTDPPA QVSVPFMSPA SAYQWFYDGY PTFGEHKQEK DLEYGACPNN MMGTFSVRTV GS SKSKYPL VVRIYMRMKH VRAWIPRPMR NQNYLFKANP NYAGNSIKPT GTSRSAITTL UniProtKB: Genome polyprotein |
-Macromolecule #2: VP2
Macromolecule | Name: VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus A71 |
Molecular weight | Theoretical: 27.81225 KDa |
Sequence | String: SPSAEACGYS DRVAQLTIGN STITTQEAAN IIVGYGEWPS YCSDDDATAV DKPTRPDVSV NRFYTLDTKL WEKSSKGWYW KFPDVLTET GVFGQNAQFH YLYRSGFCIH VQCNASKFHQ GALLVAILPE YVIGTVAGGT GTEDSHPPYK QTQPGADGFE L QHPYVLDA ...String: SPSAEACGYS DRVAQLTIGN STITTQEAAN IIVGYGEWPS YCSDDDATAV DKPTRPDVSV NRFYTLDTKL WEKSSKGWYW KFPDVLTET GVFGQNAQFH YLYRSGFCIH VQCNASKFHQ GALLVAILPE YVIGTVAGGT GTEDSHPPYK QTQPGADGFE L QHPYVLDA GIPISQLTVC HHQRINLRTN NCATIIVPYM NTLPFDSALN HCNFGLLVVP ISPLDFDQGA TPVIPITITL AP MCSEFAG LRQAVTQ UniProtKB: Genome polyprotein |
-Macromolecule #3: VP3
Macromolecule | Name: VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A |
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Source (natural) | Organism: Enterovirus A71 |
Molecular weight | Theoretical: 26.540332 KDa |
Sequence | String: GFPTELKPGT NQFLTTDDGV SAPILPNFHP TPCIHIPGEV RNLLELCQVE TILEVNNVPT NATSLMERLR FPVSAQAGKG ELCAVFRAD PGRDGPWQST MLGQLCGYYT QWSGSLEVTF MFTGSFMATG KMLIAYTPPG GPLPKDRATA MLGTHVIWDF G LQSSVTLV ...String: GFPTELKPGT NQFLTTDDGV SAPILPNFHP TPCIHIPGEV RNLLELCQVE TILEVNNVPT NATSLMERLR FPVSAQAGKG ELCAVFRAD PGRDGPWQST MLGQLCGYYT QWSGSLEVTF MFTGSFMATG KMLIAYTPPG GPLPKDRATA MLGTHVIWDF G LQSSVTLV IPWISNTHYR AHARDGVFDY YTTGLVSIWY QTNYVVPIGA PNTAYIIALA AAQKNFTMKL CKDTSHILQT AS IQ UniProtKB: Genome polyprotein |
-Macromolecule #4: VP4
Macromolecule | Name: VP4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A |
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Source (natural) | Organism: Enterovirus A71 |
Molecular weight | Theoretical: 7.501162 KDa |
Sequence | String: MGSQVSTQRS GSHENSNSAT EGSTINYTTI NYYKDSYAAT AGKQSLKQDP DKFANPVKDI FTEMAAPLK UniProtKB: Genome polyprotein |
-Macromolecule #5: SPHINGOSINE
Macromolecule | Name: SPHINGOSINE / type: ligand / ID: 5 / Number of copies: 1 / Formula: SPH |
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Molecular weight | Theoretical: 299.492 Da |
Chemical component information | ChemComp-SPH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 44.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 75125 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |