2ijo

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{{Seed}}
 
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[[Image:2ijo.png|left|200px]]
 
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==Crystal Structure of the West Nile virus NS2B-NS3 protease complexed with bovine pancreatic trypsin inhibitor==
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The line below this paragraph, containing "STRUCTURE_2ijo", creates the "Structure Box" on the page.
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<StructureSection load='2ijo' size='340' side='right'caption='[[2ijo]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2ijo]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/West_Nile_virus West Nile virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IJO FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ijo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ijo OCA], [https://pdbe.org/2ijo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ijo RCSB], [https://www.ebi.ac.uk/pdbsum/2ijo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ijo ProSAT]</span></td></tr>
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{{STRUCTURE_2ijo| PDB=2ijo | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/POLG_WNV POLG_WNV] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref> 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 JAK1 and TYK2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).<ref>PMID:15367621</ref> <ref>PMID:15956546</ref> <ref>PMID:17267492</ref> <ref>PMID:20106931</ref> <ref>PMID:19850911</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ij/2ijo_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ijo ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The two-component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication. Here, we report the crystal structure of WNV NS2B-NS3pro both in a substrate-free form and in complex with the trypsin inhibitor aprotinin/BPTI. We show that aprotinin binds in a substrate-mimetic fashion in which the productive conformation of the protease is fully formed, providing evidence for an "induced fit" mechanism of catalysis and allowing us to rationalize the distinct substrate specificities of WNV and DV proteases. We also show that the NS2B cofactor of WNV can adopt two very distinct conformations and that this is likely to be a general feature of flaviviral proteases, providing further opportunities for regulation. Finally, by comparing the flaviviral proteases with the more distantly related Hepatitis C virus, we provide insights into the evolution of the Flaviviridae fold. Our work should expedite the design of protease inhibitors to treat a range of flaviviral infections.
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===Crystal Structure of the West Nile virus NS2B-NS3 protease complexed with bovine pancreatic trypsin inhibitor===
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Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold.,Aleshin AE, Shiryaev SA, Strongin AY, Liddington RC Protein Sci. 2007 May;16(5):795-806. Epub 2007 Mar 30. PMID:17400917<ref>PMID:17400917</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2ijo" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17400917}}, adds the Publication Abstract to the page
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*[[BPTI 3D structures|BPTI 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17400917 is the PubMed ID number.
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*[[Virus protease 3D structures|Virus protease 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_17400917}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2IJO is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/West_nile_virus West nile virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IJO OCA].
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==Reference==
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Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold., Aleshin AE, Shiryaev SA, Strongin AY, Liddington RC, Protein Sci. 2007 May;16(5):795-806. Epub 2007 Mar 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17400917 17400917]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Flavivirin]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: West Nile virus]]
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[[Category: West nile virus]]
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[[Category: Aleshin AE]]
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[[Category: Aleshin, A E.]]
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[[Category: Liddington RC]]
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[[Category: Liddington, R C.]]
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[[Category: Shiryaev SA]]
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[[Category: Shiryaev, S A.]]
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[[Category: Strongin AY]]
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[[Category: Strongin, A Y.]]
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[[Category: Aprotinin]]
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[[Category: Bpti]]
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[[Category: Flavivirus]]
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[[Category: Ns2b]]
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[[Category: Ns3]]
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[[Category: Protease]]
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[[Category: Serine protease]]
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[[Category: West nile virus]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:03:11 2008''
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Current revision

Crystal Structure of the West Nile virus NS2B-NS3 protease complexed with bovine pancreatic trypsin inhibitor

PDB ID 2ijo

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