6q8j: Difference between revisions

Latest revision as of 11:55, 24 January 2024

Nterminal domain of human SMU1 in complex with LSP641

Structural highlights

6q8j is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	XS4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SMU1_HUMAN

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Destabilization of the human RED-SMU1 splicing complex as a basis for host-directed antiinfluenza strategy. Proc Natl Acad Sci U S A. 2019 May 10. pii: 1901214116. doi:, 10.1073/pnas.1901214116. PMID:31076555 doi:https://dx.doi.org/10.1073/pnas.1901214116

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OCA

[1] 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. Destabilization of the human RED-SMU1 splicing complex as a basis for host-directed antiinfluenza strategy. Proc Natl Acad Sci U S A. 2019 May 10. pii: 1901214116. doi:, 10.1073/pnas.1901214116. PMID:31076555 doi:https://dx.doi.org/10.1073/pnas.1901214116

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6q8j' size='340' side='right'caption='[[6q8j]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6q8j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMU1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
-<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>
+== Function ==
+[https://www.uniprot.org/uniprot/SMU1_HUMAN SMU1_HUMAN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ashraf, U]]
+[[Category: Ashraf U]]
-[[Category: Busca, P]]
+[[Category: Busca P]]
-[[Category: Corre, L Le]]
+[[Category: Crepin T]]
-[[Category: Crepin, T]]
+[[Category: Fournier G]]
-[[Category: Fournier, G]]
+[[Category: Gravier-Pelletier C]]
-[[Category: Gravier-Pelletier, C]]
+[[Category: Jacob Y]]
-[[Category: Jacob, Y]]
+[[Category: Le Corre L]]
-[[Category: McCarthy, A A]]
+[[Category: McCarthy AA]]
-[[Category: Naffakh, N]]
+[[Category: Naffakh N]]
-[[Category: Pietrancosta, N]]
+[[Category: Pietrancosta N]]
-[[Category: Rameix-Welti, M A]]
+[[Category: Rameix-Welti M-A]]
-[[Category: Ruigrok, R W.H]]
+[[Category: Ruigrok RWH]]
-[[Category: Tengo, L]]
+[[Category: Tengo L]]
-[[Category: Vidalain, P O]]
+[[Category: Vidalain P-O]]
-[[Category: Influenza virus]]
-[[Category: Splicing]]
-[[Category: Splicing factor]]

6q8j: Difference between revisions

Latest revision as of 11:55, 24 January 2024

Nterminal domain of human SMU1 in complex with LSP641

Structural highlights

Function

Publication Abstract from PubMed

References

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