6e6v: Difference between revisions
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<StructureSection load='6e6v' size='340' side='right'caption='[[6e6v]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='6e6v' size='340' side='right'caption='[[6e6v]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6e6v]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6e6v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/California/04/2009(H1N1)) Influenza A virus (A/California/04/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E6V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWA:3-hydroxy-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic+acid'>HWA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWA:3-hydroxy-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic+acid'>HWA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6e6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e6v OCA], [https://pdbe.org/6e6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e6v RCSB], [https://www.ebi.ac.uk/pdbsum/6e6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e6v ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/C3W5S0_I09A0 C3W5S0_I09A0] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cohen | [[Category: Cohen SM]] | ||
[[Category: Credille | [[Category: Credille CV]] | ||
[[Category: Dick | [[Category: Dick BL]] | ||
[[Category: Morrison | [[Category: Morrison CN]] | ||
Latest revision as of 09:20, 11 October 2023
The N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 3-hydroxy-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acidThe N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 3-hydroxy-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid
Structural highlights
FunctionPublication Abstract from PubMedSignificant efforts have been reported on the development of influenza antivirals including inhibitors of the RNA-dependent RNA polymerase PA N-terminal (PAN) endonuclease. Based on recently identified, highly active metal-binding pharmacophores (MBPs) for PAN endonuclease inhibition, a fragment-based drug development campaign was pursued. Guided by coordination chemistry and structure-based drug design, MBP scaffolds were elaborated to improve activity and selectivity. Structure-activity relationships were established and used to generate inhibitors of influenza endonuclease with tight-binding affinities. The activity of these inhibitors was analyzed using a fluorescence-quenching-based nuclease activity assay, and binding was validated using differential scanning fluorometry. Lead compounds were found to be highly selective for PAN endonuclease against several related dinuclear and mononuclear metalloenzymes. Combining principles of bioinorganic and medicinal chemistry in this study has resulted in some of the most active in vitro influenza PAN endonuclease inhibitors with high ligand efficiencies. SAR Exploration of Tight-Binding Inhibitors of Influenza Virus PA Endonuclease.,Credille CV, Morrison CN, Stokes RW, Dick BL, Feng Y, Sun J, Chen Y, Cohen SM J Med Chem. 2019 Nov 14;62(21):9438-9449. doi: 10.1021/acs.jmedchem.9b00747. Epub, 2019 Oct 17. PMID:31536340[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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