5des: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==2009 H1N1 PA endonuclease domain== | ==2009 H1N1 PA endonuclease domain== | ||
<StructureSection load='5des' size='340' side='right' caption='[[5des]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='5des' size='340' side='right'caption='[[5des]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5des]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DES FirstGlance]. <br> | <table><tr><td colspan='2'>[[5des]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/I09a0 I09a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DES FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cgv|5cgv]], [[5ccy|5ccy]], [[5cl0|5cl0]], [[5d2o|5d2o]], [[5d42|5d42]], [[5d4g|5d4g]], [[5d9j|5d9j]], [[5czn|5czn]], [[5d8u|5d8u]], [[5dbs|5dbs]], [[5deb|5deb]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cgv|5cgv]], [[5ccy|5ccy]], [[5cl0|5cl0]], [[5d2o|5d2o]], [[5d42|5d42]], [[5d4g|5d4g]], [[5d9j|5d9j]], [[5czn|5czn]], [[5d8u|5d8u]], [[5dbs|5dbs]], [[5deb|5deb]]</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=641501 I09A0])</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=5des FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5des OCA], [http://pdbe.org/5des PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5des RCSB], [http://www.ebi.ac.uk/pdbsum/5des PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5des ProSAT]</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=5des FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5des OCA], [http://pdbe.org/5des PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5des RCSB], [http://www.ebi.ac.uk/pdbsum/5des PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5des ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 21: | Line 22: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: I09a0]] | |||
[[Category: Large Structures]] | |||
[[Category: Kumar, G]] | [[Category: Kumar, G]] | ||
[[Category: White, S W]] | [[Category: White, S W]] | ||
Revision as of 19:03, 11 December 2019
2009 H1N1 PA endonuclease domain2009 H1N1 PA endonuclease domain
Structural highlights
Publication Abstract from PubMedThe influenza endonuclease is an essential subdomain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for antiinfluenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this drug did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitor-resistant influenza strains. Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor.,Song MS, Kumar G, Shadrick WR, Zhou W, Jeevan T, Li Z, Slavish PJ, Fabrizio TP, Yoon SW, Webb TR, Webby RJ, White SW Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3669-74. doi:, 10.1073/pnas.1519772113. Epub 2016 Mar 14. PMID:26976575[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||