7y42 - Revision history

OCA at 04:01, 8 September 2022

2022-09-08T04:01:44Z

←Older revision		Revision as of 04:01, 8 September 2022
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	<StructureSection load='7y42' size='340' side='right'caption='[[7y42]], [[Resolution\|resolution]] 3.45Å' scene=''>		<StructureSection load='7y42' size='340' side='right'caption='[[7y42]], [[Resolution\|resolution]] 3.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7y42]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y42 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7y42]] is a 3 chain structure with sequence from [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=7Y42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y42 FirstGlance]. <br>
	</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>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</scene></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>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</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=7y42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y42 OCA], [https://pdbe.org/7y42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y42 RCSB], [https://www.ebi.ac.uk/pdbsum/7y42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y42 ProSAT]</span></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=7y42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y42 OCA], [https://pdbe.org/7y42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y42 RCSB], [https://www.ebi.ac.uk/pdbsum/7y42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y42 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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]	+	[[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Wang, L~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: ~~Xiang, Y~~]]	+	[[Category: Wang L]]
-	[[Category: ~~Viral protein-inhibitor complex~~]]	+	[[Category: Xiang Y]]

OCA at 05:05, 3 August 2022

2022-08-03T05:05:28Z

←Older revision		Revision as of 05:05, 3 August 2022
Line 1:		Line 1:

	==Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with all-trans retinoic acid==		==Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with all-trans retinoic acid==
-	<StructureSection load='7y42' size='340' side='right'caption='[[7y42]]' scene=''>	+	<StructureSection load='7y42' size='340' side='right'caption='[[7y42]], [[Resolution\|resolution]] 3.45Å' 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=7Y42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y42 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7y42]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y42 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=7y42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y42 OCA], [https://pdbe.org/7y42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y42 RCSB], [https://www.ebi.ac.uk/pdbsum/7y42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y42 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>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</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=7y42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y42 OCA], [https://pdbe.org/7y42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y42 RCSB], [https://www.ebi.ac.uk/pdbsum/7y42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y42 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 ==
		+	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. IMPORTANCE Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA. Here, we found that ATRA showed potent antiviral activity against all SARS-CoV-2 variants by directly binding in a deep hydrophobic pocket of the receptor binding domain (RBD) located on top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation, suggesting the pharmacological feasibility of using ATRA or its derivatives as a remedy for and prevention of COVID-19 disease.
		+
		+	A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry.,Tong L, Wang L, Liao S, Xiao X, Qu J, Wu C, Zhu Y, Tai W, Huang Y, Wang P, Li L, Zhang R, Xiang Y, Cheng G mBio. 2022 Jul 13:e0148522. doi: 10.1128/mbio.01485-22. PMID:35862773<ref>PMID:35862773</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7y42" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lin W~~]]	+	[[Category: Wang, L]]
-	[[Category: ~~Ye X~~]]	+	[[Category: Xiang, Y]]
		+	[[Category: Viral protein-inhibitor complex]]

OCA at 16:16, 6 July 2022

2022-07-06T16:16:07Z

←Older revision		Revision as of 16:16, 6 July 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7y42 is ON HOLD~~	+	==Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with all-trans retinoic acid==
-		+	<StructureSection load='7y42' size='340' side='right'caption='[[7y42]]' scene=''>
-	~~Authors: Ye, X., Lin, W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y42 FirstGlance]. <br>
-	~~Description:~~ Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with all-trans retinoic acid	+	</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=7y42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y42 OCA], [https://pdbe.org/7y42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y42 RCSB], [https://www.ebi.ac.uk/pdbsum/7y42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y42 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Lin, W]]	+	__TOC__
-	[[Category: Ye, X]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lin W]]
		+	[[Category: Ye X]]

OCA at 06:07, 29 June 2022

2022-06-29T06:07:48Z

←Older revision		Revision as of 06:07, 29 June 2022
Line 5:		Line 5:
	Authors: Ye, X., Lin, W.		Authors: Ye, X., Lin, W.

-	Description: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with ~~ATRA~~	+	Description: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with all-trans retinoic acid
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Lin, W]]		[[Category: Lin, W]]
	[[Category: Ye, X]]		[[Category: Ye, X]]

OCA: Protected "7y42" [edit=sysop:move=sysop]

2022-06-22T07:04:55Z

Protected "7y42" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:04, 22 June 2022

OCA: New page: '''Unreleased structure''' The entry 7y42 is ON HOLD Authors: Ye, X., Lin, W. Description: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with ATRA [[Category: Unrel...

2022-06-22T07:04:54Z

New page: '''Unreleased structure''' The entry 7y42 is ON HOLD Authors: Ye, X., Lin, W. Description: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with ATRA [[Category: Unrel...

New page

'''Unreleased structure'''

The entry 7y42 is ON HOLD

Authors: Ye, X., Lin, W.

Description: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in complex with ATRA
[[Category: Unreleased Structures]]
[[Category: Lin, W]]
[[Category: Ye, X]]