7ru8 - Revision history

OCA at 07:03, 14 September 2022

OCA — Wed, 14 Sep 2022 07:03:25 GMT

←Older revision		Revision as of 07:03, 14 September 2022
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	==CC6.30 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (RBD/Fv local refinement)==		==CC6.30 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (RBD/Fv local refinement)==
-	<StructureSection load='7ru8' size='340' side='right'caption='[[7ru8]]' scene=''>	+	<StructureSection load='7ru8' size='340' side='right'caption='[[7ru8]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RU8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ru8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7RU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RU8 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=7ru8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ru8 OCA], [https://pdbe.org/7ru8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ru8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ru8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ru8 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7ru8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ru8 OCA], [https://pdbe.org/7ru8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ru8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ru8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ru8 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2]] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref> mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here we used a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduces the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity-matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for anti-viral indications would benefit from affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.
		+
		+	TITLE: Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways.,Zhao F, Keating C, Ozorowski G, Shaabani N, Francino-Urdaniz IM, Barman S, Limbo O, Burns A, Zhou P, Ricciardi MJ, Woehl J, Tran Q, Turner HL, Peng L, Huang D, Nemazee D, Andrabi R, Sok D, Teijaro JR, Whitehead TA, Ward AB, Burton DR, Jardine JG iScience. 2022 Aug 11:104914. doi: 10.1016/j.isci.2022.104914. PMID:35971553<ref>PMID:35971553</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ru8" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
	[[Category: Ozorowski G]]		[[Category: Ozorowski G]]
	[[Category: Turner HL]]		[[Category: Turner HL]]
	[[Category: Ward AB]]		[[Category: Ward AB]]

OCA at 09:54, 31 August 2022

OCA — Wed, 31 Aug 2022 09:54:41 GMT

←Older revision		Revision as of 09:54, 31 August 2022
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-	====	+	==CC6.30 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (RBD/Fv local refinement)==
	<StructureSection load='7ru8' size='340' side='right'caption='[[7ru8]]' scene=''>		<StructureSection load='7ru8' size='340' side='right'caption='[[7ru8]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RU8 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=7ru8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ru8 OCA], [https://pdbe.org/7ru8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ru8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ru8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ru8 ProSAT]</span></td></tr>		</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=7ru8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ru8 OCA], [https://pdbe.org/7ru8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ru8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ru8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ru8 ProSAT]</span></td></tr>
	</table>		</table>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Ozorowski G]]
		+	[[Category: Turner HL]]
		+	[[Category: Ward AB]]

OCA at 04:48, 25 August 2022

OCA — Thu, 25 Aug 2022 04:48:25 GMT

←Older revision		Revision as of 04:48, 25 August 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7ru8 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7ru8' size='340' side='right'caption='[[7ru8]]' scene=''>
-	~~Authors~~: ~~Ozorowski, G~~.~~, Turner, H~~.L.~~, Ward, A~~.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~CC6~~.~~30 fragment antigen binding in complex with SARS~~-~~CoV-2-6P-Mut7 S protein (RBD~~/~~Fv local refinement)~~	+	</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=7ru8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ru8 OCA], [https://pdbe.org/7ru8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ru8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ru8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ru8 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Ward~~, A.B]]	+	__TOC__
-	[[Category: ~~Ozorowski, G~~]]	+	</StructureSection>
-	[[Category: ~~Turner, H.L~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 10:21, 13 October 2021

OCA — Wed, 13 Oct 2021 10:21:11 GMT

←Older revision		Revision as of 10:21, 13 October 2021
Line 5:		Line 5:
	Authors: Ozorowski, G., Turner, H.L., Ward, A.B.		Authors: Ozorowski, G., Turner, H.L., Ward, A.B.

-	Description: CC6.30 fragment antigen binding in complex with SARS-2-CoV-6P-Mut7 S protein (RBD/Fv local refinement)	+	Description: CC6.30 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (RBD/Fv local refinement)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Ward, A.B]]		[[Category: Ward, A.B]]
	[[Category: Ozorowski, G]]		[[Category: Ozorowski, G]]
	[[Category: Turner, H.L]]		[[Category: Turner, H.L]]

OCA at 05:35, 22 September 2021

OCA — Wed, 22 Sep 2021 05:35:02 GMT

←Older revision		Revision as of 05:35, 22 September 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ru8 is ON HOLD	+	The entry 7ru8 is ON HOLD until Paper Publication

	Authors: Ozorowski, G., Turner, H.L., Ward, A.B.		Authors: Ozorowski, G., Turner, H.L., Ward, A.B.

OCA: Protected "7ru8" [edit=sysop:move=sysop]

OCA — Wed, 25 Aug 2021 05:18:24 GMT

Protected "7ru8" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:18, 25 August 2021

OCA: New page: '''Unreleased structure''' The entry 7ru8 is ON HOLD Authors: Ozorowski, G., Turner, H.L., Ward, A.B. Description: CC6.30 fragment antigen binding in complex with SARS-2-CoV-6P-Mut7 S ...

OCA — Wed, 25 Aug 2021 05:18:23 GMT

New page: '''Unreleased structure''' The entry 7ru8 is ON HOLD Authors: Ozorowski, G., Turner, H.L., Ward, A.B. Description: CC6.30 fragment antigen binding in complex with SARS-2-CoV-6P-Mut7 S ...

New page

'''Unreleased structure'''

The entry 7ru8 is ON HOLD

Authors: Ozorowski, G., Turner, H.L., Ward, A.B.

Description: CC6.30 fragment antigen binding in complex with SARS-2-CoV-6P-Mut7 S protein (RBD/Fv local refinement)
[[Category: Unreleased Structures]]
[[Category: Ward, A.B]]
[[Category: Ozorowski, G]]
[[Category: Turner, H.L]]