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 with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6Q8J FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6q8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q8j OCA], [https://pdbe.org/6q8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q8j RCSB], [https://www.ebi.ac.uk/pdbsum/6q8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q8j ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SMU1_HUMAN SMU1_HUMAN] | |||
<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> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6q8j" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Gravier-Pelletier | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ashraf U]] | ||
[[Category: | [[Category: Busca P]] | ||
[[Category: | [[Category: Crepin T]] | ||
[[Category: | [[Category: Fournier G]] | ||
[[Category: | [[Category: Gravier-Pelletier C]] | ||
[[Category: | [[Category: Jacob Y]] | ||
[[Category: | [[Category: Le Corre L]] | ||
[[Category: McCarthy AA]] | |||
[[Category: Naffakh N]] | |||
[[Category: Pietrancosta N]] | |||
[[Category: Rameix-Welti M-A]] | |||
[[Category: Ruigrok RWH]] | |||
[[Category: Tengo L]] | |||
[[Category: Vidalain P-O]] | |||
Latest revision as of 11:55, 24 January 2024
Nterminal domain of human SMU1 in complex with LSP641
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