2m9p: Difference between revisions
New page: '''Unreleased structure''' The entry 2m9p is ON HOLD Authors: Gibbs, A., Tounge, B., Steele, R. Description: NMR structure of an inhibitor bound dengue NS3 protease |
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The | ==NMR structure of an inhibitor bound dengue NS3 protease== | ||
<StructureSection load='2m9p' size='340' side='right'caption='[[2m9p]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2m9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2_Thailand/0168/1979 Dengue virus 2 Thailand/0168/1979]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M9P FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=M9P:AMINO{[(4S,5S)-4-AMINO-6,6,6-TRIFLUORO-5-HYDROXYHEXYL]AMINO}METHANIMINIUM'>M9P</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=PRD_001171:Serine+protease+inhibitor+BEZ-NLE-LYS-ARG-M9P'>PRD_001171</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9p OCA], [https://pdbe.org/2m9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m9p RCSB], [https://www.ebi.ac.uk/pdbsum/2m9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m9p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/POLG_DEN28 POLG_DEN28] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity). | |||
==See Also== | |||
*[[Virus protease 3D structures|Virus protease 3D structures]] | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dengue virus 2 Thailand/0168/1979]] | |||
[[Category: Large Structures]] | |||
[[Category: Gibbs A]] | |||
[[Category: Steele R]] | |||
[[Category: Tounge B]] | |||