6q8j: Difference between revisions
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==Nterminal domain of human SMU1 in complex with LSP641== | |||
<StructureSection load='6q8j' size='340' side='right'caption='[[6q8j]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6q8j]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q8J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q8J FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XS4:1-~{tert}-butyl-3-[6-(3,5-dimethoxyphenyl)-2-[[1-[1-(phenylmethyl)piperidin-4-yl]-1,2,3-triazol-4-yl]methylamino]pyrido[2,3-d]pyrimidin-7-yl]urea'>XS4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6q8f|6q8f]], [[6q8i|6q8i]]</td></tr> | |||
<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=6q8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q8j OCA], [http://pdbe.org/6q8j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q8j RCSB], [http://www.ebi.ac.uk/pdbsum/6q8j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q8j ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
New therapeutic strategies targeting influenza are actively sought due to limitations in current drugs available. Host-directed therapy is an emerging concept to target host functions involved in pathogen life cycles and/or pathogenesis, rather than pathogen components themselves. From this perspective, we focused on an essential host partner of influenza viruses, the RED-SMU1 splicing complex. Here, we identified two synthetic molecules targeting an alpha-helix/groove interface essential for RED-SMU1 complex assembly. We solved the structure of the SMU1 N-terminal domain in complex with RED or bound to one of the molecules identified to disrupt this complex. We show that these compounds inhibiting RED-SMU1 interaction also decrease endogenous RED-SMU1 levels and inhibit viral mRNA splicing and viral multiplication, while preserving cell viability. Overall, our data demonstrate the potential of RED-SMU1 destabilizing molecules as an antiviral therapy that could be active against a wide range of influenza viruses and be less prone to drug resistance. | |||
Destabilization of the human RED-SMU1 splicing complex as a basis for host-directed antiinfluenza strategy.,Ashraf U, Tengo L, Le Corre L, Fournier G, Busca P, McCarthy AA, Rameix-Welti MA, Gravier-Pelletier C, Ruigrok RWH, Jacob Y, Vidalain PO, Pietrancosta N, Crepin T, Naffakh N Proc Natl Acad Sci U S A. 2019 May 10. pii: 1901214116. doi:, 10.1073/pnas.1901214116. PMID:31076555<ref>PMID:31076555</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6q8j" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Ashraf, U]] | |||
[[Category: Busca, P]] | |||
[[Category: Corre, L Le]] | |||
[[Category: Crepin, T]] | [[Category: Crepin, T]] | ||
[[Category: Fournier, G]] | [[Category: Fournier, G]] | ||
[[Category: | [[Category: Gravier-Pelletier, C]] | ||
[[Category: | [[Category: Jacob, Y]] | ||
[[Category: McCarthy, A A]] | |||
[[Category: Naffakh, N]] | [[Category: Naffakh, N]] | ||
[[Category: Pietrancosta, N]] | [[Category: Pietrancosta, N]] | ||
[[Category: | [[Category: Rameix-Welti, M A]] | ||
[[Category: | [[Category: Ruigrok, R W.H]] | ||
[[Category: Tengo, L]] | |||
[[Category: Vidalain, P O]] | |||
[[Category: Influenza virus]] | |||
[[Category: Splicing]] | |||
[[Category: Splicing factor]] | |||
Revision as of 06:58, 23 May 2019
Nterminal domain of human SMU1 in complex with LSP641
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