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Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues
by
Chen, Chun-Liang
, Klose, Thomas
, Rossmann, Michael G.
, Hasan, S. Saif
, Buda, Geeta
, Klimstra, William B.
, Sun, Yingyuan
, Sun, Chengqun
in
Animals
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ Binding sites
/ Binding Sites - drug effects
/ Biological Sciences
/ Biophysics and Computational Biology
/ Cell Line
/ Chondroitin Sulfates - pharmacology
/ Cryoelectron Microscopy
/ Drug Design
/ Eastern equine encephalitis
/ Electrostatic properties
/ Encephalitis
/ Encephalitis Virus, Eastern Equine - metabolism
/ Encephalitis Virus, Eastern Equine - ultrastructure
/ Encephalomyelitis, Equine - drug therapy
/ Encephalomyelitis, Equine - virology
/ Glycoproteins
/ Heparan sulfate
/ Heparan Sulfate Proteoglycans - analogs & derivatives
/ Heparan Sulfate Proteoglycans - metabolism
/ Heparin
/ Heparin - metabolism
/ Heparin - ultrastructure
/ Horses
/ Humans
/ Icosahedral phase
/ Mesocricetus
/ Molecular Structure
/ Neurovirulence
/ PNAS Plus
/ Proteoglycans
/ Residues
/ Spikes
/ Structure-Activity Relationship
/ Sulfates
/ Viral envelope proteins
/ Viral Envelope Proteins - metabolism
/ Viral Envelope Proteins - ultrastructure
/ Virus Attachment - drug effects
/ Viruses
2020
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Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues
by
Chen, Chun-Liang
, Klose, Thomas
, Rossmann, Michael G.
, Hasan, S. Saif
, Buda, Geeta
, Klimstra, William B.
, Sun, Yingyuan
, Sun, Chengqun
in
Animals
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ Binding sites
/ Binding Sites - drug effects
/ Biological Sciences
/ Biophysics and Computational Biology
/ Cell Line
/ Chondroitin Sulfates - pharmacology
/ Cryoelectron Microscopy
/ Drug Design
/ Eastern equine encephalitis
/ Electrostatic properties
/ Encephalitis
/ Encephalitis Virus, Eastern Equine - metabolism
/ Encephalitis Virus, Eastern Equine - ultrastructure
/ Encephalomyelitis, Equine - drug therapy
/ Encephalomyelitis, Equine - virology
/ Glycoproteins
/ Heparan sulfate
/ Heparan Sulfate Proteoglycans - analogs & derivatives
/ Heparan Sulfate Proteoglycans - metabolism
/ Heparin
/ Heparin - metabolism
/ Heparin - ultrastructure
/ Horses
/ Humans
/ Icosahedral phase
/ Mesocricetus
/ Molecular Structure
/ Neurovirulence
/ PNAS Plus
/ Proteoglycans
/ Residues
/ Spikes
/ Structure-Activity Relationship
/ Sulfates
/ Viral envelope proteins
/ Viral Envelope Proteins - metabolism
/ Viral Envelope Proteins - ultrastructure
/ Virus Attachment - drug effects
/ Viruses
2020
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Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues
by
Chen, Chun-Liang
, Klose, Thomas
, Rossmann, Michael G.
, Hasan, S. Saif
, Buda, Geeta
, Klimstra, William B.
, Sun, Yingyuan
, Sun, Chengqun
in
Animals
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ Binding sites
/ Binding Sites - drug effects
/ Biological Sciences
/ Biophysics and Computational Biology
/ Cell Line
/ Chondroitin Sulfates - pharmacology
/ Cryoelectron Microscopy
/ Drug Design
/ Eastern equine encephalitis
/ Electrostatic properties
/ Encephalitis
/ Encephalitis Virus, Eastern Equine - metabolism
/ Encephalitis Virus, Eastern Equine - ultrastructure
/ Encephalomyelitis, Equine - drug therapy
/ Encephalomyelitis, Equine - virology
/ Glycoproteins
/ Heparan sulfate
/ Heparan Sulfate Proteoglycans - analogs & derivatives
/ Heparan Sulfate Proteoglycans - metabolism
/ Heparin
/ Heparin - metabolism
/ Heparin - ultrastructure
/ Horses
/ Humans
/ Icosahedral phase
/ Mesocricetus
/ Molecular Structure
/ Neurovirulence
/ PNAS Plus
/ Proteoglycans
/ Residues
/ Spikes
/ Structure-Activity Relationship
/ Sulfates
/ Viral envelope proteins
/ Viral Envelope Proteins - metabolism
/ Viral Envelope Proteins - ultrastructure
/ Virus Attachment - drug effects
/ Viruses
2020
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Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues
Journal Article
Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues
2020
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Overview
Eastern equine encephalitis virus (EEEV), a mosquito-borne icosahedral alphavirus found mainly in North America, causes human and equine neurotropic infections. EEEV neurovirulence is influenced by the interaction of the viral envelope protein E2 with heparan sulfate (HS) proteoglycans from the host’s plasma membrane during virus entry. Here, we present a 5.8-Å cryoelectron microscopy (cryo-EM) structure of EEEV complexed with the HS analog heparin. “Peripheral” HS binding sites were found to be associated with the base of each of the E2 glycoproteins that form the 60 quasi-threefold spikes (q3) and the 20 sites associated with the icosahedral threefold axes (i3). In addition, there is one HS site at the vertex of each q3 and i3 spike (the “axial” sites). Both the axial and peripheral sites are surrounded by basic residues, suggesting an electrostatic mechanism for HS binding. These residues are highly conserved among EEEV strains, and therefore a change in these residues might be linked to EEEV neurovirulence.
Publisher
National Academy of Sciences
Subject
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ Binding Sites - drug effects
/ Biophysics and Computational Biology
/ Chondroitin Sulfates - pharmacology
/ Encephalitis Virus, Eastern Equine - metabolism
/ Encephalitis Virus, Eastern Equine - ultrastructure
/ Encephalomyelitis, Equine - drug therapy
/ Encephalomyelitis, Equine - virology
/ Heparan Sulfate Proteoglycans - analogs & derivatives
/ Heparan Sulfate Proteoglycans - metabolism
/ Heparin
/ Horses
/ Humans
/ Residues
/ Spikes
/ Structure-Activity Relationship
/ Sulfates
/ Viral Envelope Proteins - metabolism
/ Viral Envelope Proteins - ultrastructure
/ Virus Attachment - drug effects
/ Viruses
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