4m5u
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4m5u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Lima/WRAIR1695P/2009(H1N1)) Influenza A virus (A/Lima/WRAIR1695P/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M5U FirstGlance]. <br> | <table><tr><td colspan='2'>[[4m5u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Lima/WRAIR1695P/2009(H1N1)) Influenza A virus (A/Lima/WRAIR1695P/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M5U FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=20F:5-(4-FLUOROPHENYL)-3-HYDROXY-6-[4-(1H-TETRAZOL-5-YL)PHENYL]PYRIDIN-2(1H)-ONE'>20F</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=20F:5-(4-FLUOROPHENYL)-3-HYDROXY-6-[4-(1H-TETRAZOL-5-YL)PHENYL]PYRIDIN-2(1H)-ONE'>20F</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=4m5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m5u OCA], [https://pdbe.org/4m5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m5u RCSB], [https://www.ebi.ac.uk/pdbsum/4m5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m5u ProSAT]</span></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=4m5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m5u OCA], [https://pdbe.org/4m5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m5u RCSB], [https://www.ebi.ac.uk/pdbsum/4m5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m5u ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is recognized as an attractive target for the development of new agents for the treatment of influenza infection. Our earlier study employing small molecule fragment screening using a high-resolution crystal form of pandemic 2009 H1N1 influenza A endonuclease domain (PAN) resulted in the identification of 5-chloro-3-hydroxypyridin-2(1H)-one as a bimetal chelating ligand at the active site of the enzyme. In the present study, several phenyl substituted 3-hydroxypyridin-2(1H)-one compounds were synthesized and evaluated for their ability to inhibit the endonuclease activity as measured by a high-throughput fluorescence assay. Two of the more potent compounds in this series, 16 and 18, had IC50 values of 11 and 23nM in the enzymatic assay, respectively. Crystal structures revealed that these compounds had distinct binding modes that chelate the two active site metal ions (M1 and M2) using only two chelating groups. The SAR and the binding mode of these 3-hydroxypyridin-2-ones provide a basis for developing a new class of anti-influenza drugs. | ||
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| - | Phenyl substituted 3-hydroxypyridin-2(1H)-ones: inhibitors of influenza A endonuclease.,Parhi AK, Xiang A, Bauman JD, Patel D, Vijayan RS, Das K, Arnold E, Lavoie EJ Bioorg Med Chem. 2013 Nov 1;21(21):6435-46. doi: 10.1016/j.bmc.2013.08.053. Epub , 2013 Sep 4. PMID:24055080<ref>PMID:24055080</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4m5u" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
5-(4-FLUOROPHENYL)-3-HYDROXY-6-[4-(1H-1,2,3,4-TETRAZOL-5-YL)PHENYL]-1,2-DIHYDROPYRIDIN-2-ONE bound to influenza 2009 pH1N1 endonuclease
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Categories: Large Structures | Arnold E | Bauman JD | Das K | Patel D
