9fiz
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the F13 protein (mutant A295E) of Vaccinia virus== | |
| + | <StructureSection load='9fiz' size='340' side='right'caption='[[9fiz]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9fiz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus_Western_Reserve Vaccinia virus Western Reserve]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FIZ 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=9fiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fiz OCA], [https://pdbe.org/9fiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fiz RCSB], [https://www.ebi.ac.uk/pdbsum/9fiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fiz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PG057_VACCW PG057_VACCW] Major envelope protein that plays a role in the biogenesis of the viral double membrane and in egress of virus from the host cell (PubMed:17475658, PubMed:27466413, PubMed:8999886). Produces the wrapped form of virus that is required for cell-to-cell spread (PubMed:27466413, PubMed:29540596). Acts as a lipase with broad specificity including phospholipase C, phospholipase A, and triacylglycerol lipase activities (PubMed:9405398).<ref>PMID:17475658</ref> <ref>PMID:27466413</ref> <ref>PMID:29540596</ref> <ref>PMID:8999886</ref> <ref>PMID:9405398</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mpox is a zoonotic disease endemic to Central and West Africa. Since 2022, two human-adapted monkeypox virus (MPXV) strains have caused large outbreaks outside these regions. Tecovirimat is the most widely used drug to treat mpox. It blocks viral egress by targeting the viral phospholipase F13; however, the structural details are unknown, and mutations in the F13 gene can result in resistance against tecovirimat, raising public health concerns. Here we report the structure of an F13 homodimer using X-ray crystallography, both alone (2.1 A) and in complex with tecovirimat (2.6 A). Combined with molecular dynamics simulations and dimerization assays, we show that tecovirimat acts as a molecular glue that promotes dimerization of the phospholipase. Tecovirimat resistance mutations identified in clinical MPXV isolates map to the F13 dimer interface and prevent drug-induced dimerization in solution and in cells. These findings explain how tecovirimat works, allow for better monitoring of resistant MPXV strains and pave the way for developing more potent and resilient therapeutics. | ||
| - | + | Structural insights into tecovirimat antiviral activity and poxvirus resistance.,Vernuccio R, Martinez Leon A, Poojari CS, Buchrieser J, Selverian CN, Jaleta Y, Meola A, Guivel-Benhassine F, Porrot F, Haouz A, Chevreuil M, Raynal B, Mercer J, Simon-Loriere E, Chandran K, Schwartz O, Hub JS, Guardado-Calvo P Nat Microbiol. 2025 Mar;10(3):734-748. doi: 10.1038/s41564-025-01936-6. Epub 2025 , Feb 12. PMID:39939832<ref>PMID:39939832</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9fiz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Vaccinia virus Western Reserve]] | ||
| + | [[Category: Guardado-Calvo P]] | ||
| + | [[Category: Vernuccio R]] | ||
Current revision
Structure of the F13 protein (mutant A295E) of Vaccinia virus
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