3vb3 - Revision history

OCA at 12:18, 8 November 2023

2023-11-08T12:18:30Z

← Older revision		Revision as of 12:18, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='3vb3' size='340' side='right'caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3vb3' size='340' side='right'caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure with sequence from [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=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EDO:1~~,2~~-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.2Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height~~: ~~3em;~~'>~~[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]~~</~~div~~></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [https://pdbe.org/3vb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3vb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vb3 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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [https://pdbe.org/3vb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3vb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vb3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/~~R1A_CVHSA R1A_CVHSA]~~] The ~~papain~~-~~like proteinase~~ (~~PL-PRO~~) ~~is responsible~~ for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host ~~IRF~~-3.<ref>PMID:~~17024178~~</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> ~~The main proteinase 3CL~~-~~PRO~~ is ~~responsible for the majority of cleavages as it cleaves~~ the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]~~. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity)~~. Also ~~contains~~ an ADP-ribose-1''-phosphate (ADRP)-~~binding function.~~<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~Nsp7-~~nsp8 ~~hexadecamer~~ may ~~possibly confer processivity to the polymerase~~, ~~maybe by binding to dsRNA or by producing~~ primers ~~utilized by the latter~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280</ref> <ref>PMID:19369340~~</ref> ~~Nsp9 is~~ a ssRNA-binding protein.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> ~~<ref>PMID:19369340</ref>~~		[https://www.uniprot.org/uniprot/R1A_SARS R1A_SARS] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).<ref>PMID:23035226</ref> <ref>PMID:30943371</ref> May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.<ref>PMID:19640993</ref> Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.<ref>PMID:16271890</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> <ref>PMID:24622840</ref> <ref>PMID:24410069</ref> Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.<ref>PMID:23943763</ref> <ref>PMID:24410069</ref> Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.[PROSITE-ProRule:PRU00772]<ref>PMID:16226257</ref> Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).<ref>PMID:24991833</ref> <ref>PMID:24410069</ref> Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref> Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref> May participate in viral replication by acting as a ssRNA-binding protein.<ref>PMID:19153232</ref> Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.<ref>PMID:22635272</ref>
	<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: ~~Chuck, C P~~]]		[[Category: Severe acute respiratory syndrome-related coronavirus]]
	[[Category: ~~Wong, K B~~]]		[[Category: Chuck CP]]
	[[Category: ~~Hydrolase~~]]		[[Category: Wong KB]]

OCA at 18:36, 27 July 2022

2022-07-27T18:36:14Z

← Older revision		Revision as of 18:36, 27 July 2022
Line 1:		Line 1:

	==Crystal structure of SARS-CoV 3C-like protease in apo form==		==Crystal structure of SARS-CoV 3C-like protease in apo form==
	<StructureSection load='3vb3' size='340' side='right' caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3vb3' size='340' side='right'caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]</~~td></tr>~~		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]</div></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b~~>~~</td><td class="sblockDat">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])~~</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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [https://pdbe.org/3vb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3vb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vb3 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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [~~http~~://pdbe.org/3vb3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vb3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vb3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>		[[https://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Cvhsa~~]]		[[Category: Large Structures]]
	[[Category: Chuck, C P]]		[[Category: Chuck, C P]]
	[[Category: Wong, K B]]		[[Category: Wong, K B]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 09:14, 5 August 2016

2016-08-05T09:14:57Z

← Older revision		Revision as of 09:14, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of SARS-CoV 3C-like protease in apo form==		==Crystal structure of SARS-CoV 3C-like protease in apo form==
	<StructureSection load='3vb3' size='340' side='right' caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3vb3' size='340' side='right' caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Sars_coronavirus Sars coronavirus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">1a ([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">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [http://www.ebi.ac.uk/pdbsum/3vb3 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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [http://pdbe.org/3vb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [http://www.ebi.ac.uk/pdbsum/3vb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vb3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3vb3" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Sars coronavirus~~]]		[[Category: Cvhsa]]
	[[Category: Chuck, C P]]		[[Category: Chuck, C P]]
	[[Category: Wong, K B]]		[[Category: Wong, K B]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 17:34, 25 December 2014

2014-12-25T17:34:50Z

← Older revision		Revision as of 17:34, 25 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~3vb3~~.~~jpg~~\|~~left~~\|~~200px~~]]		==Crystal structure of SARS-CoV 3C-like protease in apo form==
			<StructureSection load='3vb3' size='340' side='right' caption='[[3vb3]], [[Resolution\|resolution]] 2.20Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3vb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VB3 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vb4\|3vb4]], [[3vb5\|3vb5]], [[3vb6\|3vb6]], [[3vb7\|3vb7]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 SARS coronavirus])</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=3vb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vb3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vb3 RCSB], [http://www.ebi.ac.uk/pdbsum/3vb3 PDBsum]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 muM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was approximately 10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 muM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.

	~~{{STRUCTURE_3vb3\| PDB=3vb3 \| SCENE= }}~~		Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.,Chuck CP, Chen C, Ke Z, Chi-Cheong Wan D, Chow HF, Wong KB Eur J Med Chem. 2012 Nov 7;59C:1-6. doi: 10.1016/j.ejmech.2012.10.053. PMID:23202846<ref>PMID:23202846</ref>

	~~===Crystal structure~~ of ~~SARS-CoV 3C-like protease in apo form===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_23202846}}~~		== References ==
			<references/>
	==~~About this Structure~~==		__TOC__
	~~[[3vb3]] is a 2 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA].~~		</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Chuck, C P.]]		[[Category: Chuck, C P]]
	[[Category: Wong, K B.]]		[[Category: Wong, K B]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 21:08, 12 December 2012

2012-12-12T21:08:32Z

← Older revision		Revision as of 21:08, 12 December 2012
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	~~'''Unreleased structure'''~~		[[Image:3vb3.jpg\|left\|200px]]

	~~The entry~~ 3vb3 ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_3vb3\| PDB=3vb3 \| SCENE= }}

	~~Authors: Chuck, C.P., Wong, K.B.~~		===Crystal structure of SARS-CoV 3C-like protease in apo form===

	~~Description~~: ~~Crystal structure of SARS~~-~~CoV 3C-like protease in apo form~~		{{ABSTRACT_PUBMED_23202846}}

			==About this Structure==
			[[3vb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VB3 OCA].
			[[Category: Sars coronavirus]]
			[[Category: Chuck, C P.]]
			[[Category: Wong, K B.]]
			[[Category: Hydrolase]]

OCA at 06:03, 8 February 2012

2012-02-08T06:03:55Z

← Older revision		Revision as of 06:03, 8 February 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3vb3 is ON HOLD		The entry 3vb3 is ON HOLD until Paper Publication

	Authors: Chuck, C.P., Wong, K.B.		Authors: Chuck, C.P., Wong, K.B.

	Description: Crystal structure of SARS-CoV 3C-like protease in apo form		Description: Crystal structure of SARS-CoV 3C-like protease in apo form

OCA: Protected "3vb3" [edit=sysop:move=sysop]

2012-01-11T05:59:56Z

Protected "3vb3" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:59, 11 January 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 3vb3 is ON HOLD Authors: Chuck, C.P., Wong, K.B. Description: Crystal structure of SARS-CoV 3C-like protease in apo form

2012-01-11T05:59:55Z

New page: '''Unreleased structure''' The entry 3vb3 is ON HOLD Authors: Chuck, C.P., Wong, K.B. Description: Crystal structure of SARS-CoV 3C-like protease in apo form

New page

'''Unreleased structure'''

The entry 3vb3 is ON HOLD

Authors: Chuck, C.P., Wong, K.B.

Description: Crystal structure of SARS-CoV 3C-like protease in apo form