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==Crystal structure of avian influenza virus PAn bound to compound 6==
==Crystal structure of avian influenza virus PAn bound to compound 6==
<StructureSection load='4e5l' size='340' side='right' caption='[[4e5l]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
<StructureSection load='4e5l' size='340' side='right'caption='[[4e5l]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4e5l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/viet_nam/1203/2004(h5n1)) Influenza a virus (a/viet nam/1203/2004(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5L FirstGlance]. <br>
<table><tr><td colspan='2'>[[4e5l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5L FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBH:2,3-DIHYDROXY-BENZOIC+ACID'>DBH</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]] 2.469&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e5e|4e5e]], [[4e5f|4e5f]], [[4e5g|4e5g]], [[4e5h|4e5h]], [[4e5i|4e5i]], [[4e5j|4e5j]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DBH:2,3-DIHYDROXY-BENZOIC+ACID'>DBH</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=284218 Influenza A virus (A/Viet Nam/1203/2004(H5N1))])</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=4e5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5l OCA], [https://pdbe.org/4e5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5l RCSB], [https://www.ebi.ac.uk/pdbsum/4e5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5l 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=4e5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5l OCA], [http://pdbe.org/4e5l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e5l RCSB], [http://www.ebi.ac.uk/pdbsum/4e5l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5l ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q5EP34_9INFA Q5EP34_9INFA]
Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or "snatched" from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors.


Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease.,Dubois RM, Slavish PJ, Baughman BM, Yun MK, Bao J, Webby RJ, Webb TR, White SW PLoS Pathog. 2012 Aug;8(8):e1002830. Epub 2012 Aug 2. PMID:22876176<ref>PMID:22876176</ref>
==See Also==
 
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4e5l" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: DuBois, R M]]
[[Category: Large Structures]]
[[Category: Slavish, P J]]
[[Category: DuBois RM]]
[[Category: Webb, T R]]
[[Category: Slavish PJ]]
[[Category: White, S W]]
[[Category: Webb TR]]
[[Category: Endonuclease domain]]
[[Category: White SW]]
[[Category: H5n1 subtype]]
[[Category: Transcription]]
[[Category: Viral protein]]

Latest revision as of 17:53, 14 March 2024

Crystal structure of avian influenza virus PAn bound to compound 6Crystal structure of avian influenza virus PAn bound to compound 6

Structural highlights

4e5l is a 4 chain structure with sequence from Influenza A virus (A/Viet Nam/1203/2004(H5N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.469Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q5EP34_9INFA

See Also

4e5l, resolution 2.47Å

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