8fa1: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8fa1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Nostoc_punctiforme_PCC_73102 Nostoc punctiforme PCC 73102] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FA1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8fa1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Nostoc_punctiforme_PCC_73102 Nostoc punctiforme PCC 73102] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FA1 FirstGlance]. <br> | ||
</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=8fa1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fa1 OCA], [https://pdbe.org/8fa1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fa1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fa1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fa1 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.51Å</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=8fa1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fa1 OCA], [https://pdbe.org/8fa1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fa1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fa1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fa1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B2J981_NOSP7 B2J981_NOSP7] [https://www.uniprot.org/uniprot/A0A8B6RKS7_SARS2 A0A8B6RKS7_SARS2] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide inhibitors based on the Wuhan strain sequence are less efficacious. Here, we report an Omicron-specific peptide inhibitor designed based on the structure of the Omicron HR1HR2 postfusion bundle. Specifically, we inserted an additional residue in HR2 near the Omicron HR1 K969 residue to better accommodate the N969K mutation and relieve the distortion in the structure of the HR1HR2 postfusion bundle it introduced. The designed inhibitor recovers the loss of inhibition activity of the original longHR2_42 peptide with the Wuhan strain sequence against the Omicron variant in both a cell-cell fusion assay and a vesicular stomatitis virus (VSV)-SARS-CoV-2 chimera infection assay, suggesting that a similar approach could be used to combat future variants. From a mechanistic perspective, our work suggests the interactions in the extended region of HR2 may mediate the initial landing of HR2 onto HR1 during the transition of the S protein from the prehairpin intermediate to the postfusion state. | |||
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor.,Yang K, Wang C, Kreutzberger AJB, White KI, Pfuetzner RA, Esquivies L, Kirchhausen T, Brunger AT Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2300360120. doi: , 10.1073/pnas.2300360120. Epub 2023 Mar 20. PMID:36940324<ref>PMID:36940324</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8fa1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||