6q8i

Nterminal domain of human SMU1 in complex with human REDmid

spinqualitylabelsall models 6q8i, resolution 3.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q8i is a 16 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 3.17Å 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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