3e90

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:02, 30 October 2024) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3e90.png|left|200px]]
 
-
<!--
+
==West Nile vi rus NS2B-NS3protease in complexed with inhibitor Naph-KKR-H==
-
The line below this paragraph, containing "STRUCTURE_3e90", creates the "Structure Box" on the page.
+
<StructureSection load='3e90' size='340' side='right'caption='[[3e90]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[3e90]] is a 4 chain structure with sequence from [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=3E90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E90 FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NKK:N~2~-(NAPHTHALEN-2-YLCARBONYL)-L-LYSYL-N-[(1S)-4-CARBAMIMIDAMIDO-1-FORMYLBUTYL]-L-LYSINAMIDE'>NKK</scene></td></tr>
-
{{STRUCTURE_3e90| PDB=3e90 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e90 OCA], [https://pdbe.org/3e90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e90 RCSB], [https://www.ebi.ac.uk/pdbsum/3e90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e90 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[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>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/3e90_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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=3e90 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Over the last decade, West Nile virus has spread rapidly via mosquito transmission from infected migratory birds to humans. One potential therapeutic approach to treating infection is to inhibit the virally encoded serine protease that is essential for viral replication. Here we report the crystal structure of the viral NS3 protease tethered to its essential NS2B cofactor and bound to a potent substrate-based tripeptide inhibitor, 2-naphthoyl-Lys-Lys-Arg-H (K(i)=41 nM), capped at the N-terminus by 2-naphthoyl and capped at the C-terminus by aldehyde. An important and unexpected feature of this structure is the presence of two conformations of the catalytic histidine suggesting a role for ligand stabilization of the catalytically competent His conformation. Analysis of other West Nile virus NS3 protease structures and related serine proteases supports this hypothesis, suggesting that the common catalytic mechanism involves an induced-fit mechanism.
-
===West Nile vi rus NS2B-NS3protease in complexed with inhibitor Naph-KKR-H===
+
Structure of West Nile virus NS3 protease: ligand stabilization of the catalytic conformation.,Robin G, Chappell K, Stoermer MJ, Hu SH, Young PR, Fairlie DP, Martin JL J Mol Biol. 2009 Feb 6;385(5):1568-77. Epub 2008 Nov 25. PMID:19059417<ref>PMID:19059417</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3e90" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_19059417}}, adds the Publication Abstract to the page
+
*[[Virus protease 3D structures|Virus protease 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 19059417 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_19059417}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
[[Category: Large Structures]]
-
3E90 is a 4 chains structure of sequences from [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=3E90 OCA].
+
[[Category: West Nile virus]]
-
 
+
[[Category: Martin JL]]
-
==Reference==
+
[[Category: Robin G]]
-
<ref group="xtra">PMID:19059417</ref><references group="xtra"/>
+
-
[[Category: Flavivirin]]
+
-
[[Category: West nile virus]]
+
-
[[Category: Martin, J L.]]
+
-
[[Category: Robin, G.]]
+
-
[[Category: Atp-binding]]
+
-
[[Category: Capsid protein]]
+
-
[[Category: Catalytic histidine]]
+
-
[[Category: Crystal structure]]
+
-
[[Category: Helicase]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Induced fit]]
+
-
[[Category: Ns3 protease]]
+
-
[[Category: Nucleotide-binding]]
+
-
[[Category: Protease inhibitor]]
+
-
[[Category: Rna replication]]
+
-
[[Category: Transmembrane]]
+
-
[[Category: Trypsin-like serine protease]]
+
-
[[Category: Virion]]
+
-
[[Category: West nile virus]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 27 14:39:40 2009''
+

Current revision

West Nile vi rus NS2B-NS3protease in complexed with inhibitor Naph-KKR-H

PDB ID 3e90

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3e90"
Personal tools