4cb6: Difference between revisions
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==Structure of Influenza A H5N1 PB2 cap-binding domain with bound cap analogue (compound 11)== | |||
<StructureSection load='4cb6' size='340' side='right'caption='[[4cb6]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4cb6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/duck/Shantou/4610/2003(H5N1)) Influenza A virus (A/duck/Shantou/4610/2003(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CB6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=29R:2,9-N,N-DI(4-CARBOXYBUTYL)-7-N-METHYLGUANINE'>29R</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></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=4cb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cb6 OCA], [https://pdbe.org/4cb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cb6 RCSB], [https://www.ebi.ac.uk/pdbsum/4cb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cb6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q2LG68_9INFA Q2LG68_9INFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The heterotrimeric influenza virus polymerase performs replication and transcription of viral RNA in the nucleus of infected cells. Transcription by 'cap-snatching' requires that host-cell pre-mRNAs are bound via their 5' cap to the PB2 subunit. Thus, the PB2 cap binding site is potentially a good target for new antiviral drugs that will directly inhibit viral replication. Docking studies using the structure of the PB2 cap binding domain suggested that 7-alkylguanine derivatives substituted at position N-9 and N-2 could be good candidates. Four series of 7,9-di- and 2,7,9-tri-alkyl guanine derivatives were synthesized and evaluated by an AlphaScreen assay in competition with a biotinylated cap analogue. Three synthesised compounds display potent in vitro activity with IC50 lower than 10 M. High-resolution X-ray structures of three inhibitors in complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and provide detailed information for further compound optimization. | |||
New 7-methyl-guanosine derivatives targeting the influenza polymerase PB2 cap-binding domain.,Pautus S, Sehr P, Lewis J, Fortune A, Wolkerstorfer A, Szolar O, Guilligay D, Lunardi T, Decout JL, Cusack S J Med Chem. 2013 Oct 18. PMID:24134208<ref>PMID:24134208</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cb6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Cusack S]] | |||
[[Category: Decout JL]] | |||
[[Category: Fortune A]] | |||
[[Category: Gulligay D]] | |||
[[Category: Lewis J]] | |||
[[Category: Lunardi T]] | |||
[[Category: Pautus S]] | |||
[[Category: Sehr P]] | |||
[[Category: Szolar O]] | |||
[[Category: Wolkerstorfer A]] | |||
Latest revision as of 12:06, 20 December 2023
Structure of Influenza A H5N1 PB2 cap-binding domain with bound cap analogue (compound 11)
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