6oj7: Difference between revisions
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==Respiratory syncytial virus fusion glycoprotein N-terminal heptad repeat domain+VIQKI I456F== | |||
<StructureSection load='6oj7' size='340' side='right'caption='[[6oj7]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6oj7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OJ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OJ7 FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=6oj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oj7 OCA], [http://pdbe.org/6oj7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oj7 RCSB], [http://www.ebi.ac.uk/pdbsum/6oj7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oj7 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with the RSV-HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Cocrystal structures of the new Phe-substituted inhibitors coassembled with HPIV3 or RSV-HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F. | |||
Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor.,Outlaw VK, Lemke JT, Zhu Y, Gellman SH, Porotto M, Moscona A J Am Chem Soc. 2020 Jan 23. doi: 10.1021/jacs.9b11548. PMID:31951396<ref>PMID:31951396</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Outlaw, V | <div class="pdbe-citations 6oj7" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Gellman, S H]] | |||
[[Category: Outlaw, V K]] | |||
[[Category: Antiviral protein]] | |||
[[Category: Fusion inhibitor]] | |||
[[Category: Fusion protein]] | |||
[[Category: Six-helix bundle]] | |||
Revision as of 11:02, 5 February 2020
Respiratory syncytial virus fusion glycoprotein N-terminal heptad repeat domain+VIQKI I456FRespiratory syncytial virus fusion glycoprotein N-terminal heptad repeat domain+VIQKI I456F
Structural highlights
Publication Abstract from PubMedHuman parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with the RSV-HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Cocrystal structures of the new Phe-substituted inhibitors coassembled with HPIV3 or RSV-HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F. Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor.,Outlaw VK, Lemke JT, Zhu Y, Gellman SH, Porotto M, Moscona A J Am Chem Soc. 2020 Jan 23. doi: 10.1021/jacs.9b11548. PMID:31951396[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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