4oow: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==HCV NS5B polymerase with a fragment of quercetagetin== | ||
<StructureSection load='4oow' size='340' side='right' caption='[[4oow]], [[Resolution|resolution]] 2.57Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4oow]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OOW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAQ:CATECHOL'>CAQ</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=4oow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oow OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oow RCSB], [http://www.ebi.ac.uk/pdbsum/4oow PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is a key target for antiviral intervention. The goal of this study was to identify the binding site and unravel the molecular mechanism by which natural flavonoids efficiently inhibit HCV RdRp. Screening identified the flavonol quercetagetin as the most potent inhibitor of HCV RdRp activity. Quercetagetin was found to inhibit RdRp through inhibition of RNA binding to the viral polymerase, a yet unknown antiviral mechanism. X-ray crystallographic structure analysis of the RdRp-quercetagetin complex identified quercetagetin's binding site at the entrance of the RNA template tunnel, confirming its original mode of action. This antiviral mechanism was associated with a high barrier to resistance in both site-directed mutagenesis and long-term selection experiments. In conclusion, we identified a new mechanism for non-nucleoside inhibition of HCV RdRp through inhibition of RNA binding to the enzyme, a mechanism associated with broad genotypic activity and a high barrier to resistance. Our results open the way to new antiviral approaches for HCV and other viruses that use an RdRp based on RNA binding inhibition, that could prove to be useful in human, animal or plant viral infections. | |||
Inhibition of RNA binding to hepatitis C virus RNA-dependent RNA polymerase: a new mechanism for antiviral intervention.,Ahmed-Belkacem A, Guichou JF, Brillet R, Ahnou N, Hernandez E, Pallier C, Pawlotsky JM Nucleic Acids Res. 2014;42(14):9399-409. doi: 10.1093/nar/gku632. Epub 2014 Jul, 22. PMID:25053847<ref>PMID:25053847</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: RNA-directed RNA polymerase]] | |||
[[Category: Ahmed-Belkacem, A]] | |||
[[Category: Guichou, J F]] | |||
[[Category: Hernandez, E]] | |||
[[Category: Nazim, N]] | |||
[[Category: Pallier, C]] | |||
[[Category: Pawlotsky, J M]] | |||
[[Category: Rozenn, B]] | |||
[[Category: Enzyme]] | |||
[[Category: Transferase]] | |||