5wop

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<StructureSection load='5wop' size='340' side='right' caption='[[5wop]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
<StructureSection load='5wop' size='340' side='right' caption='[[5wop]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5wop]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WOP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WOP FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5wop]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9infa 9infa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WOP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WOP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eg7|5eg7]], [[4enf|4enf]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eg7|5eg7]], [[4enf|4enf]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 9INFA])</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=5wop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wop OCA], [http://pdbe.org/5wop PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wop RCSB], [http://www.ebi.ac.uk/pdbsum/5wop PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wop 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=5wop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wop OCA], [http://pdbe.org/5wop PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wop RCSB], [http://www.ebi.ac.uk/pdbsum/5wop PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wop ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique `cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10-13 nucleotides downstream from the cap. The capped RNA fragment is then used as the primer for viral mRNA transcription. The structure of PB2cap from influenza virus H1N1 A/California/07/2009 and of its complex with the cap analog m(7)GTP were solved at high resolution. Structural changes are observed in the cap-binding site of this new pandemic influenza virus strain, especially the hydrophobic interactions between the ligand and the target protein. m(7)GTP binds deeper in the pocket than some other virus strains, much deeper than the host cap-binding proteins. Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses.
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In the face of increasing drug resistance and the rapidly increasing necessity for practicality in clinical settings, drugs targeting different viral proteins are needed in order to control influenza A and B. A small molecule that tenaciously adheres to the PB2cap binding domain, part of the heterotrimeric RNA polymerase machinery of influenza A virus and influenza B virus, is a promising drug candidate. Understanding the anatomic behavior of PB2cap upon ligand binding will aid in the development of a more robust inhibitor. In this report, the anatomic behavior of the influenza A virus PB2cap domain is established by solving the crystal structure of native influenza A virus PB2cap at 1.52 A resolution. By comparing it with the ligand-bound structure, the dissociation and rotation of the ligand-binding domain in PB2cap from the C-terminal domain is identified. This domain movement is present in many PB2cap structures, suggesting its functional relevance for polymerase activity.
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The cap-binding site of influenza virus protein PB2 as a drug target.,Severin C, Rocha de Moura T, Liu Y, Li K, Zheng X, Luo M Acta Crystallogr D Struct Biol. 2016 Feb;72(Pt 2):245-53. doi:, 10.1107/S2059798316000085. Epub 2016 Jan 22. PMID:26894672<ref>PMID:26894672</ref>
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High-resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding.,Constantinides A, Gumpper R, Severin C, Luo M Acta Crystallogr F Struct Biol Commun. 2018 Mar 1;74(Pt 3):122-127. doi:, 10.1107/S2053230X18000894. Epub 2018 Feb 26. PMID:29497014<ref>PMID:29497014</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 06:57, 14 March 2018

High Resolution Structure of Mutant CA09-PB2cap

5wop, resolution 1.52Å

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