7kj5 - Revision history

OCA at 06:47, 24 February 2021

OCA — Wed, 24 Feb 2021 06:47:30 GMT

←Older revision		Revision as of 06:47, 24 February 2021
Line 1:		Line 1:

	==SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation==		==SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation==
-	<StructureSection load='7kj5' size='340' side='right'caption='[[7kj5]]~~, [[Resolution\|resolution]] 3.60Å~~' scene=''>	+	<StructureSection load='7kj5' size='340' side='right'caption='[[7kj5]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[7kj5]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KJ5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7KJ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KJ5 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></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=7kj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kj5 OCA], [https://pdbe.org/7kj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kj5 RCSB], [https://www.ebi.ac.uk/pdbsum/7kj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kj5 ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>~~	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7kj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kj5 OCA], [~~http~~://pdbe.org/7kj5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7kj5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7kj5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7kj5 ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[http://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 ==
-	Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
-
-	A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro.,Xiao T, Lu J, Zhang J, Johnson RI, McKay LGA, Storm N, Lavine CL, Peng H, Cai Y, Rits-Volloch S, Lu S, Quinlan BD, Farzan M, Seaman MS, Griffiths A, Chen B bioRxiv. 2020 Sep 18. doi: 10.1101/2020.09.18.301952. PMID:32995768<ref>PMID:32995768</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7kj5" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cai~~, Y F~~]]	+	[[Category: Cai YF]]
-	[[Category: Chen, B]]	+	[[Category: Chen B]]
-	[[Category: Xiao~~, T S~~]]	+	[[Category: Xiao TS]]
-	[[Category: Zhang, J]]	+	[[Category: Zhang J]]
-	~~[[Category: Viral protein~~]]	+

OCA at 08:31, 20 January 2021

OCA — Wed, 20 Jan 2021 08:31:08 GMT

←Older revision		Revision as of 08:31, 20 January 2021
Line 1:		Line 1:

	==SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation==		==SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation==
-	<StructureSection load='7kj5' size='340' side='right'caption='[[7kj5]]' scene=''>	+	<StructureSection load='7kj5' size='340' side='right'caption='[[7kj5]], [[Resolution\|resolution]] 3.60Å' 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=7KJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KJ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kj5]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KJ5 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kj5 OCA], [http://pdbe.org/7kj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kj5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kj5 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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kj5 OCA], [http://pdbe.org/7kj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kj5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kj5 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://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 ==
		+	Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
		+
		+	A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro.,Xiao T, Lu J, Zhang J, Johnson RI, McKay LGA, Storm N, Lavine CL, Peng H, Cai Y, Rits-Volloch S, Lu S, Quinlan BD, Farzan M, Seaman MS, Griffiths A, Chen B bioRxiv. 2020 Sep 18. doi: 10.1101/2020.09.18.301952. PMID:32995768<ref>PMID:32995768</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kj5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cai YF]]	+	[[Category: Cai, Y F]]
-	[[Category: Chen B]]	+	[[Category: Chen, B]]
-	[[Category: Xiao TS]]	+	[[Category: Xiao, T S]]
-	[[Category: Zhang J]]	+	[[Category: Zhang, J]]
		+	[[Category: Viral protein]]

OCA at 08:04, 11 November 2020

OCA — Wed, 11 Nov 2020 08:04:08 GMT

←Older revision		Revision as of 08:04, 11 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7kj5 ~~is ON HOLD~~	+	==SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation==
-		+	<StructureSection load='7kj5' size='340' side='right'caption='[[7kj5]]' scene=''>
-	~~Authors~~: ~~Zhang~~, J., ~~Xiao~~, T.S., ~~Cai, Y~~.F., ~~Chen, B~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KJ5 FirstGlance]. <br>
-	~~Description: SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kj5 OCA], [http://pdbe.org/7kj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kj5 RCSB], [http://www.ebi.ac.uk/pdbsum/7kj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kj5 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Zhang, J~~]]	+	__TOC__
-	[[Category: ~~Cai, Y.F~~]]	+	</StructureSection>
-	[[Category: Xiao~~, T.S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Chen, B~~]]	+	[[Category: Cai YF]]
		+	[[Category: Chen B]]
		+	[[Category: Xiao TS]]
		+	[[Category: Zhang J]]

OCA: Protected "7kj5" [edit=sysop:move=sysop]

OCA — Wed, 04 Nov 2020 05:37:58 GMT

Protected "7kj5" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:37, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kj5 is ON HOLD Authors: Zhang, J., Xiao, T.S., Cai, Y.F., Chen, B. Description: SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformat...

OCA — Wed, 04 Nov 2020 05:37:57 GMT

New page: '''Unreleased structure''' The entry 7kj5 is ON HOLD Authors: Zhang, J., Xiao, T.S., Cai, Y.F., Chen, B. Description: SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformat...

New page

'''Unreleased structure'''

The entry 7kj5 is ON HOLD

Authors: Zhang, J., Xiao, T.S., Cai, Y.F., Chen, B.

Description: SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation
[[Category: Unreleased Structures]]
[[Category: Zhang, J]]
[[Category: Cai, Y.F]]
[[Category: Xiao, T.S]]
[[Category: Chen, B]]