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4m5u

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Revision as of 08:17, 4 August 2016

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

Structural highlights

4m5u is a 1 chain structure with sequence from Influenza a virus (a/lima/wrair1695p/2009(h1n1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4kil, 4ln7, 4m5o, 4m5q, 4m5r, 4m5v
Gene:	PA (Influenza A virus (A/Lima/WRAIR1695P/2009(H1N1)))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[F0TRT1_9INFA] Implicated in endonuclease cleavage of capped RNA primers. Displays an elongation factor activity in viral RNA synthesis. Dispensable for viral transcription, but not replication (By similarity).[SAAS:SAAS001009_004_020464]

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Parhi AK, Xiang A, Bauman JD, Patel D, Vijayan RS, Das K, Arnold E, Lavoie EJ. Phenyl substituted 3-hydroxypyridin-2(1H)-ones: inhibitors of influenza A endonuclease. Bioorg Med Chem. 2013 Nov 1;21(21):6435-46. doi: 10.1016/j.bmc.2013.08.053. Epub , 2013 Sep 4. PMID:24055080 doi:http://dx.doi.org/10.1016/j.bmc.2013.08.053

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m5u"

@@ Line 1: / Line 1: @@
 ==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==
 <StructureSection load='4m5u' size='340' side='right' caption='[[4m5u]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kil|4kil]], [[4ln7|4ln7]], [[4m5o|4m5o]], [[4m5q|4m5q]], [[4m5r|4m5r]], [[4m5v|4m5v]]</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=985958 Influenza A virus (A/Lima/WRAIR1695P/2009(H1N1))])</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=4m5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m5u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m5u RCSB], [http://www.ebi.ac.uk/pdbsum/4m5u PDBsum]</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=4m5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m5u OCA], [http://pdbe.org/4m5u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m5u RCSB], [http://www.ebi.ac.uk/pdbsum/4m5u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m5u ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4m5u" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4m5u

From Proteopedia

Revision as of 08:17, 4 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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