6s5v
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6s5v is ON HOLD until Jul 02 2021 Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the Cap-Midlink region of the H5N1 Influenza A virus polymerase in complex with a Cap-domain binding analogue== | |
| + | <StructureSection load='6s5v' size='340' side='right'caption='[[6s5v]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6s5v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/duck/fujian/13/2002(h5n1)) Influenza a virus (a/duck/fujian/13/2002(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S5V 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>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=KWN:(1~{S},2~{S},3~{S},6~{R})-2-[[2-[5,7-bis(fluoranyl)-1~{H}-indol-3-yl]-5-fluoranyl-pyrimidin-4-yl]amino]-3,6-dimethyl-cyclohexane-1-carboxylic+acid'>KWN</scene></td></tr> | ||
| + | <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=274828 Influenza A virus (A/duck/Fujian/13/2002(H5N1))])</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=6s5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s5v OCA], [http://pdbe.org/6s5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s5v RCSB], [http://www.ebi.ac.uk/pdbsum/6s5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s5v ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/Q6E3N3_9INFA Q6E3N3_9INFA]] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062][SAAS:SAAS01041023] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In the search for novel influenza inhibitors we evaluated 7-fluoro-substituted indoles as bioisosteric replacements for the 7-azaindole scaffold of Pimodivir, a PB2 (polymerase basic protein 2) inhibitor currently in clinical development. Specifically, a 5,7-difluoroindole derivative 11a was identified as a potent and metabolically stable influenza inhibitor. 11a demonstrated a favorable oral pharmacokinetic profile and in vivo efficacy in mice. In addition, it was found that 11a was not at risk of metabolism via aldehyde oxidase, an advantage over previously described inhibitors of this class. The crystal structure of 11a bound to influenza A PB2 cap region is disclosed here and deposited to the PDB. | ||
| - | + | Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region.,McGowan DC, Balemans W, Embrechts W, Motte M, Keown JR, Buyck C, Corbera J, Funes M, Moreno L, Cooymans L, Tahri A, Eymard J, Stoops B, Strijbos R, Van den Berg J, Fodor E, Grimes JM, Koul A, Jonckers THM, Raboisson P, Guillemont J J Med Chem. 2019 Oct 30. doi: 10.1021/acs.jmedchem.9b01091. PMID:31647875<ref>PMID:31647875</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6s5v" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Fodor, E]] | ||
| + | [[Category: Grimes, J M]] | ||
| + | [[Category: Keown, J R]] | ||
| + | [[Category: Cap binding analogue]] | ||
| + | [[Category: H5n1]] | ||
| + | [[Category: Influenza some]] | ||
| + | [[Category: Influenza polymerase]] | ||
| + | [[Category: Viral protein]] | ||
Current revision
Crystal structure of the Cap-Midlink region of the H5N1 Influenza A virus polymerase in complex with a Cap-domain binding analogue
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