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 (1-4). 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
Dengue Virus Genome carries only one single strand of RNA as its genome. This genome only encodes for ten proteins (three structural and seven "production" proteins). The production proteins are useful in aiding the virus to penetrate the host cell and help produce new virus structures. The outer membrane of the protein is constructed of 180 copies of the envelope protein, which this membrane helps the virus attach to the host cell membrane.
Figure 1: This image represents the entire Dengue genome (complete with 180 copies of the envelope protein)
Dengue Virus inside Cell (1ok8) When the virus is in its infectious form the surface is smooth (figure 1), but as it is exposed to the acidic environment of the cell cytoplasm, this causes the proteins to snap into a trimeric spike (or trimer), which allows it to penetrate and fuse with the lysozome membrane of the host cell. In experimental laboratory settings, the extraction or isolation of this trimer model can be done in many different ways. The main, observed, extraction was separated by detergent isolation. The model shows a chloride ion (detergent) liganded by three amide nitrogens from Lys-110. The chloride is believed to dissolve away the liposome on the trimer tip. The tip of the trimer, or , displays three hydrophobic residues, Trp-101, Lys-107, and Phe-108. Due to this dissolution from the chloride molecule, the three-fold –clustered membrane tip does not tightly bind together and thereby does not penetrate very deep into the host cell membrane. The fusion loop is thinking to be held into the membrane by an “aromatic anchor” formed by Trp-101 and Phe-108 |
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Dengue NS5 Protein (2j7w) The NS5 protein is a 900-residue peptide, which contains a methyltransferase domain. This protein plays an important role in the Dengue virus replication. The protein not only functions as a methyltransferase, but also as a RNA polymerase (which helps replicate its RNA). The NS5 protein also contains guanylyltransferase activities, which, along with methyltransferase, help protect the viral genome and create efficient protein translation. There are four serotypes of the Dengue virus (1-4), and the NS5 protein is most prominent in the Dengue-2-serotype, helping it with its pathogenesis. Dengue-2 NS5 contains an also has an which is considered a "S-adenosyl methionine-dependent methyltransferase fold" structure. The S-adenosyl methionine (SAM) ligand is methylated in the methyltransferase domain, creating S-adenosyl-l-homocysteine ()as a by-product. The SAM and SAH are useful in aiding in the folding of the active site. In the NS5 protein, there is another binding site for GTP. This binding of GTP is done in the N-terminal domain on the protein. The is what allows the Dengue-2-methyltransferase to complete its functions; these functions include translation, transcription and replication processes. |
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Dengue NS3/NS2B Protein (2vbc) The NS3 protease is a serine protease that can also function as a RNA helicase and RTPase/NTPase. The enzymatic function of this protease is important for the Dengue virus to replicate. This enzyme of the virus is also a potential target for vaccines and antiviral drugs. The catalytic triad , is found between these two beta barrels, and its activity is dependent on the presence of the cofactor. This cofactor then wraps around the NS3 protease domain and becomes part of the active site. The NS2B cofactor is critical for proteolytic activation of the NS3 protease. The NS3 protease is made up of an extensive network of hydrogen bond and hydrophobic interaction, making it very rigid. NS2B is also important in contributing to substrate binding. This implies that NS2B acts as an enzyme activator as well as being directly involved in substrate binding/interactions. |
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