4cb6
From Proteopedia
(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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CB6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cb4|4cb4]], [[4cb5|4cb5]], [[4cb7|4cb7]]</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=4cb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cb6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cb6 RCSB], [http://www.ebi.ac.uk/pdbsum/4cb6 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <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> | |
| - | [[Category: Cusack, S | + | == References == |
| - | [[Category: Decout, J L | + | <references/> |
| - | [[Category: Fortune, A | + | __TOC__ |
| - | [[Category: Gulligay, D | + | </StructureSection> |
| - | [[Category: Lewis, J | + | [[Category: Cusack, S]] |
| - | [[Category: Lunardi, T | + | [[Category: Decout, J L]] |
| - | [[Category: Pautus, S | + | [[Category: Fortune, A]] |
| - | [[Category: Sehr, P | + | [[Category: Gulligay, D]] |
| - | [[Category: Szolar, O | + | [[Category: Lewis, J]] |
| - | [[Category: Wolkerstorfer, A | + | [[Category: Lunardi, T]] |
| + | [[Category: Pautus, S]] | ||
| + | [[Category: Sehr, P]] | ||
| + | [[Category: Szolar, O]] | ||
| + | [[Category: Wolkerstorfer, A]] | ||
[[Category: Cap-binding inhibitor]] | [[Category: Cap-binding inhibitor]] | ||
[[Category: Influenza polymerase]] | [[Category: Influenza polymerase]] | ||
[[Category: M7gtp]] | [[Category: M7gtp]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 13:20, 4 January 2015
Structure of Influenza A H5N1 PB2 cap-binding domain with bound cap analogue (compound 11)
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