5idk: Difference between revisions
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The | ==Crystal structure of West Nile Virus NS2B-NS3 protease in complex with a capped dipeptide boronate inhibitor== | ||
<StructureSection load='5idk' size='340' side='right' caption='[[5idk]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5idk]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IDK FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6A8:((R)-1-((S)-3-(4-(AMINOMETHYL)PHENYL)-2-BENZAMIDOPROPANEAMIDO)-4-GUANIDINOBUTYL)BORONIC+ACID,+CYCLIC+DOUBLE+ESTER+WITH+GLYCEROL'>6A8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
[[Category: | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5idk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5idk OCA], [http://pdbe.org/5idk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5idk RCSB], [http://www.ebi.ac.uk/pdbsum/5idk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5idk ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[[http://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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hilgenfeld, R]] | |||
[[Category: Zhang, L]] | |||
[[Category: Antivirus agent]] | |||
[[Category: Boronic acid]] | |||
[[Category: Peptide]] | |||
[[Category: Viral protein]] | |||
[[Category: West nile virus]] |
Revision as of 22:17, 15 December 2016
Crystal structure of West Nile Virus NS2B-NS3 protease in complex with a capped dipeptide boronate inhibitorCrystal structure of West Nile Virus NS2B-NS3 protease in complex with a capped dipeptide boronate inhibitor
Structural highlights
Function[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).[1] [2] [3] [4] [5] 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).[6] [7] [8] [9] [10] 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).[11] [12] [13] [14] [15] Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity).[16] [17] [18] [19] [20] Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).[21] [22] [23] [24] [25] Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).[26] [27] [28] [29] [30] 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).[31] [32] [33] [34] [35] 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).[36] [37] [38] [39] [40] Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).[41] [42] [43] [44] [45] 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).[46] [47] [48] [49] [50] 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).[51] [52] [53] [54] [55] References
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