3sci - Revision history

OCA at 10:26, 6 November 2024

2024-11-06T10:26:06Z

← Older revision		Revision as of 10:26, 6 November 2024
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	<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>~~, ~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.9Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em~~;~~'>[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>ACE2, UNQ868/PRO1885 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23]~~ </~~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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [https://pdbe.org/3sci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [https://www.ebi.ac.uk/pdbsum/3sci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci 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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [https://pdbe.org/3sci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [https://www.ebi.ac.uk/pdbsum/3sci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[https://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.		[https://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 23:
	*[[Angiotensin-Converting Enzyme 3D structures\|Angiotensin-Converting Enzyme 3D structures]]		*[[Angiotensin-Converting Enzyme 3D structures\|Angiotensin-Converting Enzyme 3D structures]]
	*[[Sandbox 3001\|Sandbox 3001]]		*[[Sandbox 3001\|Sandbox 3001]]
	*[[Spike protein\|Spike protein]]		*[[Spike protein 3D structures\|Spike protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Angiotensin-converting enzyme 2]]~~		[[Category: Homo sapiens]]
	~~[[Category: Human~~]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Geraghty, R]]		[[Category: Severe acute respiratory syndrome-related coronavirus]]
	[[Category: Li, F]]		[[Category: Geraghty R]]
	[[Category: Peng, G]]		[[Category: Li F]]
	[[Category: Wilken, M]]		[[Category: Peng G]]
	[[Category: Wu, K]]		[[Category: Wilken M]]
	~~[[Category: Beta sheet]]~~		[[Category: Wu K]]
	~~[[Category: Hydrolase-viral protein complex~~]]

OCA at 07:50, 29 June 2022

2022-06-29T07:50:52Z

OCA at 09:58, 16 September 2020

2020-09-16T09:58:31Z

← Older revision		Revision as of 09:58, 16 September 2020
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	<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://pdbe.org/3sci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://pdbe.org/3sci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[http://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.		[[http://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[http://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.

			Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus.,Wu K, Peng G, Wilken M, Geraghty RJ, Li F J Biol Chem. 2012 Mar 16;287(12):8904-11. Epub 2012 Jan 30. PMID:22291007<ref>PMID:22291007</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 3sci" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Angiotensin-Converting Enzyme 3D structures\|Angiotensin-Converting Enzyme 3D structures]]		*[[Angiotensin-Converting Enzyme 3D structures\|Angiotensin-Converting Enzyme 3D structures]]
			*[[Sandbox 3001\|Sandbox 3001]]
			*[[Spike protein\|Spike protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:38, 17 July 2019

2019-07-17T11:38:43Z

← Older revision		Revision as of 11:38, 17 July 2019
Line 1:		Line 1:

	==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==		==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==
	<StructureSection load='3sci' size='340' side='right' caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Cvhsa Cvhsa~~] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN~~]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://pdbe.org/3sci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://pdbe.org/3sci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></td></tr>
Line 14:		Line 14:

	==See Also==		==See Also==
	*[[Angiotensin-Converting Enzyme\|Angiotensin-Converting Enzyme]]		*[[Angiotensin-Converting Enzyme 3D structures\|Angiotensin-Converting Enzyme 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 20:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Angiotensin-converting enzyme 2]]		[[Category: Angiotensin-converting enzyme 2]]
	~~[[Category: Cvhsa]]~~
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Geraghty, R]]		[[Category: Geraghty, R]]
	[[Category: Li, F]]		[[Category: Li, F]]

OCA at 23:42, 4 August 2016

2016-08-04T23:42:05Z

← Older revision		Revision as of 23:42, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==		==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==
	<StructureSection load='3sci' size='340' side='right' caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3sci' size='340' side='right' caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~] and [http://en.wikipedia.org/wiki/~~Sars_coronavirus Sars coronavirus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 ~~SARS coronavirus~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum]</span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://pdbe.org/3sci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Angiotensin-converting enzyme 2]]		[[Category: Angiotensin-converting enzyme 2]]
	[[Category: ~~Homo sapiens~~]]		[[Category: Cvhsa]]
	[[Category: ~~Sars coronavirus~~]]		[[Category: Human]]
	[[Category: Geraghty, R]]		[[Category: Geraghty, R]]
	[[Category: Li, F]]		[[Category: Li, F]]

OCA at 20:48, 24 December 2014

2014-12-24T20:48:37Z

← Older revision		Revision as of 20:48, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus])</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum]</span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [http://www.ebi.ac.uk/pdbsum/3sci PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[http://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.

	==See Also==		==See Also==
	*[[Angiotensin-Converting Enzyme\|Angiotensin-Converting Enzyme]]		*[[Angiotensin-Converting Enzyme\|Angiotensin-Converting Enzyme]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
Line 17:		Line 21:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Geraghty, R.]]		[[Category: Geraghty, R]]
	[[Category: Li, F.]]		[[Category: Li, F]]
	[[Category: Peng, G.]]		[[Category: Peng, G]]
	[[Category: Wilken, M.]]		[[Category: Wilken, M]]
	[[Category: Wu, K.]]		[[Category: Wu, K]]
	[[Category: Beta sheet]]		[[Category: Beta sheet]]
	[[Category: Hydrolase-viral protein complex]]		[[Category: Hydrolase-viral protein complex]]

OCA at 05:26, 5 June 2014

2014-06-05T05:26:32Z

@@ Line 1: / Line 1: @@
-[[Image:3sci.jpg|left|200px]]
+==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==
-<!--
+==See Also==
-The line below this paragraph, containing "STRUCTURE_3sci", creates the "Structure Box" on the page.
+*[[Angiotensin-Converting Enzyme|Angiotensin-Converting Enzyme]]
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+__TOC__
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+</StructureSection>
 [[Category: Angiotensin-converting enzyme 2]]
 [[Category: Homo sapiens]]

OCA at 06:39, 8 February 2012

2012-02-08T06:39:28Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3sci.jpg|left|200px]]
-The entry 3sci is ON HOLD  until Paper Publication
+<!--
-Authors: Wu, K., Peng, G., Wilken, M., Geraghty, R., Li, F.
+===Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2===
-Description: Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2

OCA at 05:38, 27 July 2011

2011-07-27T05:38:02Z

← Older revision		Revision as of 05:38, 27 July 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3sci is ON HOLD		The entry 3sci is ON HOLD until Paper Publication

	Authors: Wu, K., Peng, G., Wilken, M., Geraghty, R., Li, F.		Authors: Wu, K., Peng, G., Wilken, M., Geraghty, R., Li, F.

	Description: Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2		Description: Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2

OCA at 16:20, 22 June 2011

2011-06-22T16:20:56Z

← Older revision		Revision as of 16:20, 22 June 2011
Line 3:		Line 3:
	The entry 3sci is ON HOLD		The entry 3sci is ON HOLD

	Authors: ~~Kailang~~ Wu, ~~Guiqing~~ Peng, ~~Matthew~~ Wilken, ~~Robert~~ Geraghty, ~~Fang~~ Li		Authors: Wu, K., Peng, G., Wilken, M., Geraghty, R., Li, F.

	Description: Crystal structure of ~~human angiotensin-converting enzyme 2 complexed with the~~ receptor-binding domain of a predicted SARS coronavirus human strain		Description: Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2

← Older revision		Revision as of 07:50, 29 June 2022
Line 3:		Line 3:
	<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/ ] and [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>		<table><tr><td colspan='2'>[[3sci]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ajf\|2ajf]], [[3scj\|3scj]], [[3sck\|3sck]], [[3scl\|3scl]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ACE2, UNQ868/PRO1885 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2 Angiotensin-converting enzyme 2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.23 3.4.17.23] </span></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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [~~http~~://pdbe.org/3sci PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3sci PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci 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=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [https://pdbe.org/3sci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [https://www.ebi.ac.uk/pdbsum/3sci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[~~http~~://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.		[[https://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[https://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==