Sandbox 1k4r
Dengue VirusDengue Virus
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| 1k4r, resolution 24.00Å () | |||||||||
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| Related: | 1svb | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure of Dengue VirusStructure of Dengue Virus
The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map. The virus core, within a lipid bilayer, has a less-ordered structure than the external, icosahedral scaffold of 90 glycoprotein E dimers. The three E monomers per icosahedral asymmetric unit do not have quasiequivalent symmetric environments. Difference maps indicate the location of the small membrane protein M relative to the overlaying scaffold of E dimers. The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal beta barrels of domain II of the glycoprotein E are inserted into the cellular membrane.
Structure of dengue virus: implications for flavivirus organization, maturation, and fusion., Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J, Lenches E, Jones CT, Mukhopadhyay S, Chipman PR, Strauss EG, Baker TS, Strauss JH, Cell. 2002 Mar 8;108(5):717-25. PMID:11893341
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
EtiologyEtiology
Dengue virus is a mosquito borne illness and is a major threat in most of the tropical and sub-tropical countries around the world. There are four related subtypes of the Dengue virus. Dengue is not transmitted directly from person-to-person and symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. There is no vaccine or any specific medicine to treat dengue. People who have dengue fever should rest, drink plenty of fluids and reduce the fever using paracetamol or see a doctor.
About this StructureAbout this Structure
In the infectious form of the virus, the envelope protein lays flat on the surface of the virus, forming a smooth coat with icosahedral symmetry. However, when the virus is carried into the cell and into lysozomes, the acidic environment causes the protein to snap into a different shape, assembling into trimeric spike Several hydrophobic amino acids at the tip of this spike, colored bright red here, insert into the lysozomal membrane and cause the virus membrane to fuse with lysozome. The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-Å resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus
Asp-663 and Asp-664 from motif C of the catalytic site are shown in stick representation and labeled. high GTP concentration or Mn2+ was necessary for DENV NS5 RNA synthesis
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