4ovz - Revision history

OCA at 07:06, 27 September 2023

OCA — Wed, 27 Sep 2023 07:06:27 GMT

←Older revision		Revision as of 07:06, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/SARS_coronavirus_Urbani SARS coronavirus Urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/SARS_coronavirus_Urbani SARS coronavirus Urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [https://pdbe.org/4ovz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [https://www.ebi.ac.uk/pdbsum/4ovz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovz 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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [https://pdbe.org/4ovz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [https://www.ebi.ac.uk/pdbsum/4ovz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovz ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:48, 25 January 2023

OCA — Wed, 25 Jan 2023 07:48:24 GMT

←Older revision		Revision as of 07:48, 25 January 2023
Line 3:		Line 3:
	<StructureSection load='4ovz' size='340' side='right'caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ovz' size='340' side='right'caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Sars_coronavirus_urbani Sars~~ coronavirus ~~urbani~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/SARS_coronavirus_Urbani SARS coronavirus Urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [https://pdbe.org/4ovz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [https://www.ebi.ac.uk/pdbsum/4ovz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovz 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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [~~http~~://pdbe.org/4ovz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ovz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovz 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_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: ~~Sars~~ coronavirus ~~urbani~~]]	+	[[Category: SARS coronavirus Urbani]]
-	[[Category: Baez-Santos~~, Y M~~]]	+	[[Category: Baez-Santos YM]]
-	[[Category: Mesecar, A]]	+	[[Category: Mesecar A]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Coronavirus]]~~	+
-	~~[[Category: Cov]]~~	+
-	~~[[Category: Deubiquitinating enzyme]]~~	+
-	~~[[Category: Dub]]~~	+
-	~~[[Category: Hcov]]~~	+
-	~~[[Category: Human coronavirus]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Mer]]~~	+
-	~~[[Category: Middle east respiratory syndrome]]~~	+
-	~~[[Category: Plpro]]~~	+
-	~~[[Category: Protease inhibitor]]~~	+
-	~~[[Category: Sar]]~~	+
-	~~[[Category: Severe acute respiratory syndrome~~]]	+

OCA at 07:52, 19 February 2020

OCA — Wed, 19 Feb 2020 07:52:39 GMT

←Older revision		Revision as of 07:52, 19 February 2020
Line 1:		Line 1:

	==X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases==		==X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases==
-	<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4ovz' size='340' side='right'caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_urbani Sars coronavirus urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_urbani Sars coronavirus urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Sars coronavirus urbani]]		[[Category: Sars coronavirus urbani]]
	[[Category: Baez-Santos, Y M]]		[[Category: Baez-Santos, Y M]]

OCA at 15:54, 11 August 2016

OCA — Thu, 11 Aug 2016 15:54:28 GMT

←Older revision		Revision as of 15:54, 11 August 2016
Line 1:		Line 1:
		+
	==X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases==		==X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases==
	<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz 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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://pdbe.org/4ovz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4ovz" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:55, 24 December 2014

OCA — Wed, 24 Dec 2014 11:55:25 GMT

←Older revision		Revision as of 11:55, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_urbani Sars coronavirus urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_urbani Sars coronavirus urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz 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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</span></td></tr>
-	<table>	+	</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 22:
	</StructureSection>		</StructureSection>
	[[Category: Sars coronavirus urbani]]		[[Category: Sars coronavirus urbani]]
-	[[Category: Baez-Santos, Y M.]]	+	[[Category: Baez-Santos, Y M]]
-	[[Category: Mesecar, A.]]	+	[[Category: Mesecar, A]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Coronavirus]]		[[Category: Coronavirus]]

OCA at 06:20, 11 June 2014

OCA — Wed, 11 Jun 2014 06:20:24 GMT

←Older revision		Revision as of 06:20, 11 June 2014
Line 2:		Line 2:
	<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>	+	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_urbani Sars coronavirus urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVZ FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>		<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</span></td></tr>
	<table>		<table>
Line 14:		Line 13:
	X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases.,Baez-Santos YM, Barraza SJ, Wilson MW, Agius MP, Mielech AM, Davis NM, Baker SC, Larsen SD, Mesecar AD J Med Chem. 2014 Mar 27;57(6):2393-412. doi: 10.1021/jm401712t. Epub 2014 Mar 14. PMID:24568342<ref>PMID:24568342</ref>		X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases.,Baez-Santos YM, Barraza SJ, Wilson MW, Agius MP, Mielech AM, Davis NM, Baker SC, Larsen SD, Mesecar AD J Med Chem. 2014 Mar 27;57(6):2393-412. doi: 10.1021/jm401712t. Epub 2014 Mar 14. PMID:24568342<ref>PMID:24568342</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 20:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Sars coronavirus urbani]]
	[[Category: Baez-Santos, Y M.]]		[[Category: Baez-Santos, Y M.]]
	[[Category: Mesecar, A.]]		[[Category: Mesecar, A.]]

OCA at 09:42, 1 May 2014

OCA — Thu, 01 May 2014 09:42:02 GMT

←Older revision		Revision as of 09:42, 1 May 2014
Line 2:		Line 2:
	<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>	+	<table><tr><td colspan='2'>[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>
-	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
-	<b>[[Non-Standard_Residue\|NonStd Res:]]</b> <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene><br>	+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>
-	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>	+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
-	<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</span><br>	+	<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=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.		Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.
Line 13:		Line 15:

	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:15, 30 April 2014

OCA — Wed, 30 Apr 2014 10:15:51 GMT

←Older revision		Revision as of 10:15, 30 April 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>		[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>
		+	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P85:N-[(4-FLUOROPHENYL)METHYL]-1-[(1R)-1-NAPHTHALEN-1-YLETHYL]PIPERIDINE-4-CARBOXAMIDE'>P85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<b>[[Non-Standard_Residue\|NonStd Res:]]</b> <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene><br>
	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>		<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
		+	<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ovz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ovz RCSB], [http://www.ebi.ac.uk/pdbsum/4ovz PDBsum]</span><br>
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.		Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.

OCA at 05:18, 30 April 2014

OCA — Wed, 30 Apr 2014 05:18:29 GMT

←Older revision		Revision as of 05:18, 30 April 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ovz\| PDB=4ovz \| SCENE= }}~~	+	==X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases==
-	===X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases===	+	<StructureSection load='4ovz' size='340' side='right' caption='[[4ovz]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24568342}}~~	+	== Structural highlights ==
		+	[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]. <br>
		+	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
		+	== Publication Abstract from PubMed ==
		+	Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold preference for the coronaviral enzyme over homologous human deubiquitinating enzymes (DUBs), and no significant cytotoxicity in Vero E6 and HEK293 cell lines is observed. X-ray structural analyses of inhibitor-bound crystal structures revealed subtle differences between binding modes of the initial benzodioxolane lead (15g) and the most potent analogues 3k and 3j, featuring a monofluoro substitution at para and meta positions of the benzyl ring, respectively. Finally, the less lipophilic bis(amide) 3e and methoxypyridine 5c exhibit significantly improved metabolic stability and are viable candidates for advancing to in vivo studies.

-	~~==Function==~~	+	X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases.,Baez-Santos YM, Barraza SJ, Wilson MW, Agius MP, Mielech AM, Davis NM, Baker SC, Larsen SD, Mesecar AD J Med Chem. 2014 Mar 27;57(6):2393-412. doi: 10.1021/jm401712t. Epub 2014 Mar 14. PMID:24568342<ref>PMID:24568342</ref>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4ovz]] is~~ a ~~2 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA]~~.	+	== References ==
-		+	<references/>
-	==~~Reference~~==	+	__TOC__
-	~~<ref group="xtra">PMID:024568342</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</StructureSection>
	[[Category: Baez-Santos, Y M.]]		[[Category: Baez-Santos, Y M.]]
	[[Category: Mesecar, A.]]		[[Category: Mesecar, A.]]

OCA at 07:38, 23 April 2014

OCA — Wed, 23 Apr 2014 07:38:48 GMT

←Older revision		Revision as of 07:38, 23 April 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4ovz\| PDB=4ovz \| SCENE= }}
		+	===X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-Like Proteases===
		+	{{ABSTRACT_PUBMED_24568342}}

-	The ~~entry 4ovz~~ is ~~ON HOLD~~	+	==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>

-	~~Authors~~: ~~Baez-Santos, Y~~.M.~~, Mesecar, A~~.	+	==About this Structure==
		+	[[4ovz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OVZ OCA].

-	~~Description~~: X-~~Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human~~ Coronavirus ~~Papain~~-~~Like Proteases~~	+	==Reference==
		+	<ref group="xtra">PMID:024568342</ref><references group="xtra"/><references/>
		+	[[Category: Baez-Santos, Y M.]]
		+	[[Category: Mesecar, A.]]
		+	[[Category: Complex]]
		+	[[Category: Coronavirus]]
		+	[[Category: Cov]]
		+	[[Category: Deubiquitinating enzyme]]
		+	[[Category: Dub]]
		+	[[Category: Hcov]]
		+	[[Category: Human coronavirus]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Mer]]
		+	[[Category: Middle east respiratory syndrome]]
		+	[[Category: Plpro]]
		+	[[Category: Protease inhibitor]]
		+	[[Category: Sar]]
		+	[[Category: Severe acute respiratory syndrome]]