6nel: Difference between revisions
New page: '''Unreleased structure''' The entry 6nel is ON HOLD Authors: Bauman, J.D., Arnold, E. Description: 4-(2-(4-fluorophenyl)-5-hydroxy-6-oxo-1,6-dihydropyridin-3-yl)benzoic acid bound to ... |
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==4-(2-(4-fluorophenyl)-5-hydroxy-6-oxo-1,6-dihydropyridin-3-yl)benzoic acid bound to influenza 2009 pH1N1 endonuclease== | |||
<StructureSection load='6nel' size='340' side='right'caption='[[6nel]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6nel]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Luxembourg/43/2009(H1N1)) Influenza A virus (A/Luxembourg/43/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NEL 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KKV:4-[2-(4-fluorophenyl)-5-hydroxy-6-oxo-1,6-dihydropyridin-3-yl]benzoic+acid'>KKV</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6nel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nel OCA], [https://pdbe.org/6nel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nel RCSB], [https://www.ebi.ac.uk/pdbsum/6nel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nel ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C6H0Y9_9INFA C6H0Y9_9INFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Seasonal influenza infections are associated with an estimated 250-500,000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A strains. These data have prompted research on inhibitors that target the cap-snatching endonuclease activity of PA. Xofluza, baloxavir marboxil, recently approved for clinical use, inhibits cap-snatching endonuclease. Resistance to Xofluza has been reported in both in vitro systems and in the clinic. A X-ray crystallographic screening campaign of a fragment library targeting the IAV endonuclease enzyme identified 5-chloro-3-hydroxypyridin-2(1H)-one as a bimetal chelating ligand at the active site. We have reported the structure-activity relationships for 3-hydroxypyridin-2(1H)-ones and 3-hydroxyquinolin-2(1H)-ones as endonuclease inhibitors. These studies identified two distinct binding metal modes associated with inhibition of this enzyme that are influenced by the presence of substituents on the phenyl groups at the 5- and 6-positions of 3-hydroxypyridin(1H)-2-ones. We report herein on the structure-activity relationships associated with various para-substituted 5-phenyl derivatives of 6-(p-fluorophenyl)-3-hydroxypyridin (1H)-2-one and the effect of using naphthyl, benzyl, and napthylmethyl groups as alternatives to the p-fluorophenyl substituent on their activity as endonuclease inhibitors. | |||
Aryl and arylalkyl substituted 3-hydroxypyridin(1H)-2-ones: Synthesis and evaluation as inhibitors of influenza A endonuclease.,LaVoie EJ, Sagong HY, Bauman JD, Nogales A, Martinez-Sobrido L, Arnold E ChemMedChem. 2019 Apr 14. doi: 10.1002/cmdc.201900084. PMID:30983160<ref>PMID:30983160</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Arnold | <div class="pdbe-citations 6nel" style="background-color:#fffaf0;"></div> | ||
[[Category: Bauman | |||
==See Also== | |||
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Arnold E]] | |||
[[Category: Bauman JD]] | |||