5w3i: Difference between revisions
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==Crystal structure of the influenza virus PA endonuclease in complex with inhibitor 6e (SRI-29685)== | ==Crystal structure of the influenza virus PA endonuclease in complex with inhibitor 6e (SRI-29685)== | ||
<StructureSection load='5w3i' size='340' side='right' caption='[[5w3i]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='5w3i' size='340' side='right'caption='[[5w3i]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5w3i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3I FirstGlance]. <br> | <table><tr><td colspan='2'>[[5w3i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/I09a0 I09a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3I FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GY5:5-hydroxy-N-(2-methoxyethyl)-6-oxo-2-[(2S)-1-(phenoxyacetyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide'>GY5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GY5:5-hydroxy-N-(2-methoxyethyl)-6-oxo-2-[(2S)-1-(phenoxyacetyl)pyrrolidin-2-yl]-1,6-dihydropyrimidine-4-carboxamide'>GY5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=641501 I09A0])</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=5w3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3i OCA], [http://pdbe.org/5w3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w3i RCSB], [http://www.ebi.ac.uk/pdbsum/5w3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3i 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=5w3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3i OCA], [http://pdbe.org/5w3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w3i RCSB], [http://www.ebi.ac.uk/pdbsum/5w3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3i ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5w3i" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5w3i" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[RNA polymerase|RNA polymerase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: I09a0]] | |||
[[Category: Large Structures]] | |||
[[Category: Kumar, G]] | [[Category: Kumar, G]] | ||
[[Category: White, S W]] | [[Category: White, S W]] | ||
Revision as of 20:28, 11 December 2019
Crystal structure of the influenza virus PA endonuclease in complex with inhibitor 6e (SRI-29685)Crystal structure of the influenza virus PA endonuclease in complex with inhibitor 6e (SRI-29685)
Structural highlights
Publication Abstract from PubMedInfluenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease.,Beylkin D, Kumar G, Zhou W, Park J, Jeevan T, Lagisetti C, Harfoot R, Webby RJ, White SW, Webb TR Sci Rep. 2017 Dec 7;7(1):17139. doi: 10.1038/s41598-017-17419-6. PMID:29215062[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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