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3kwi

From Proteopedia

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{{STRUCTURE_3kwi| PDB=3kwi | SCENE= }}
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==X-ray structure of NS1 effector domain W187Y mutant==
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===X-ray structure of NS1 effector domain W187Y mutant===
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<StructureSection load='3kwi' size='340' side='right' caption='[[3kwi]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19995550}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3kwi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KWI FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ee9|3ee9]], [[3ee8|3ee8]], [[3kwg|3kwg]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</td></tr>
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<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=3kwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kwi RCSB], [http://www.ebi.ac.uk/pdbsum/3kwi PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The influenza A virus nonstructural protein NS1 is a multifunctional dimeric protein that acts as a potent inhibitor of the host cellular antiviral state. The C-terminal effector domain of NS1 binds host proteins, including CPSF30, and is a target for the development of new antiviral drugs. Here we present crystallographic structures of two mutant effector domains, W187Y and W187A, of influenza A/Udorn/72 virus. Unlike wild-type, the mutants behave exclusively as monomers in solution based on gel filtration data and light scattering. The W187Y mutant is able to bind CPSF30 with a binding affinity close to the wild-type protein; that is, it retains a receptor site for aromatic ligands nearly identical to the wild-type. Therefore, this monomeric mutant protein could serve as a drug target for a high throughput inhibitor screening assays, since its binding pocket is unoccupied in solution and potentially more accessible to small molecule ligands.
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==Function==
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X-ray structures of NS1 effector domain mutants.,Xia S, Robertus JD Arch Biochem Biophys. 2010 Feb 15;494(2):198-204. Epub 2009 Dec 6. PMID:19995550<ref>PMID:19995550</ref>
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[[http://www.uniprot.org/uniprot/NS1_I72A2 NS1_I72A2]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref> Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3kwi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWI OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019995550</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Influenza a virus]]
[[Category: Influenza a virus]]
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[[Category: Robertus, J D.]]
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[[Category: Robertus, J D]]
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[[Category: Xia, S.]]
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[[Category: Xia, S]]
[[Category: Effector domain]]
[[Category: Effector domain]]
[[Category: Host cytoplasm]]
[[Category: Host cytoplasm]]

Revision as of 17:47, 18 December 2014

X-ray structure of NS1 effector domain W187Y mutant

3kwi, resolution 2.21Å

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