4m0w - Revision history

OCA at 14:39, 8 November 2023

2023-11-08T14:39:46Z

←Older revision		Revision as of 14:39, 8 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] 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=4M0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M0W FirstGlance]. <br>		<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] 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=4M0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M0W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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]] 1.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [https://pdbe.org/4m0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [https://www.ebi.ac.uk/pdbsum/4m0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0w 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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [https://pdbe.org/4m0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [https://www.ebi.ac.uk/pdbsum/4m0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0w ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:45, 21 December 2022

2022-12-21T10:45:56Z

←Older revision		Revision as of 10:45, 21 December 2022
Line 1:		Line 1:

	==Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin==		==Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin==
-	<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4m0w' size='340' side='right'caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [~~http~~://en.wikipedia.org/wiki/~~Cvhsa Cvhsa~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4M0W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] 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=4M0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M0W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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">1a, NSP3 ([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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [https://pdbe.org/4m0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [https://www.ebi.ac.uk/pdbsum/4m0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0w 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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [~~http~~://pdbe.org/4m0w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4m0w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0w 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> [[http://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in ~~DNA repair; Lys~~-~~11-linked is involved in ERAD (endoplasmic reticulum-associated degradation)~~ and ~~in cell~~-~~cycle regulation; Lys~~-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. ~~Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however,~~ in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.	+	[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 ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[~~Ubiquitin~~\|~~Ubiquitin~~]]	+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
		+	*[[3D structures of ubiquitin\|3D structures of ubiquitin]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
-	[[Category: ~~Cvhsa~~]]	+	[[Category: Large Structures]]
-	[[Category: Chen, H Y]]	+	[[Category: Severe acute respiratory syndrome-related coronavirus]]
-	[[Category: Cheng, S C]]	+	[[Category: Chen H-Y]]
-	[[Category: Chou, C Y]]	+	[[Category: Cheng S-C]]
-	[[Category: Chou, Y W]]	+	[[Category: Chou C-Y]]
-	[[Category: Lai, H Y]]	+	[[Category: Chou Y-W]]
-	~~[[Category: Hydrolase-protein binding complex]]~~	+	[[Category: Lai H-Y]]
-	~~[[Category: Papain-like protease-ubiquitin complex]]~~	+
-	~~[[Category: Protein hydrolase and deubiquitination~~]]	+

OCA at 00:55, 5 August 2016

2016-08-05T00:55:55Z

←Older revision		Revision as of 00:55, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin==		==Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin==
	<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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">1a, NSP3 ([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">1a, NSP3 ([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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w 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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://pdbe.org/4m0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0w 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 4m0w" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 21:23, 24 December 2014

2014-12-24T21:23:39Z

←Older revision		Revision as of 21:23, 24 December 2014
Line 2:		Line 2:
	<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. <br>	+	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M0W FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">1a, NSP3 ([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">1a, NSP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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 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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w 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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w 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> [[http://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 14:		Line 15:
	Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease.,Chou CY, Lai HY, Chen HY, Cheng SC, Cheng KW, Chou YW Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):572-81. doi:, 10.1107/S1399004713031040. Epub 2014 Jan 31. PMID:24531491<ref>PMID:24531491</ref>		Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease.,Chou CY, Lai HY, Chen HY, Cheng SC, Cheng KW, Chou YW Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):572-81. doi:, 10.1107/S1399004713031040. Epub 2014 Jan 31. PMID:24531491<ref>PMID:24531491</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>
		+
		+	==See Also==
		+	*[[Ubiquitin\|Ubiquitin]]
	== References ==		== References ==
	<references/>		<references/>
Line 22:		Line 26:
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Cvhsa]]		[[Category: Cvhsa]]
-	[[Category: Chen, H Y.]]	+	[[Category: Chen, H Y]]
-	[[Category: Cheng, S C.]]	+	[[Category: Cheng, S C]]
-	[[Category: Chou, C Y.]]	+	[[Category: Chou, C Y]]
-	[[Category: Chou, Y W.]]	+	[[Category: Chou, Y W]]
-	[[Category: Lai, H Y.]]	+	[[Category: Lai, H Y]]
	[[Category: Hydrolase-protein binding complex]]		[[Category: Hydrolase-protein binding complex]]
	[[Category: Papain-like protease-ubiquitin complex]]		[[Category: Papain-like protease-ubiquitin complex]]
	[[Category: Protein hydrolase and deubiquitination]]		[[Category: Protein hydrolase and deubiquitination]]

OCA at 09:40, 1 May 2014

2014-05-01T09:40:13Z

←Older revision		Revision as of 09:40, 1 May 2014
Line 2:		Line 2:
	<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. <br>	+	<table><tr><td colspan='2'>[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. <br>
-	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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>	+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">1a, NSP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr>
-	<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w PDBsum]</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>
		+	<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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 A resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.		Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 A resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.
Line 12:		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 10:13, 30 April 2014

2014-04-30T10:13:59Z

←Older revision		Revision as of 10:13, 30 April 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. <br>		[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]. <br>
		+	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4m0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m0w RCSB], [http://www.ebi.ac.uk/pdbsum/4m0w PDBsum]</span><br>
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 A resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.		Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 A resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.

OCA at 05:28, 30 April 2014

2014-04-30T05:28:27Z

←Older revision		Revision as of 05:28, 30 April 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4m0w\| PDB=4m0w \| SCENE= }}~~	+	==Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin==
-	===Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin===	+	<StructureSection load='4m0w' size='340' side='right' caption='[[4m0w]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W 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 ==
		+	Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 A resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.

-	~~==Function==~~	+	Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease.,Chou CY, Lai HY, Chen HY, Cheng SC, Cheng KW, Chou YW Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):572-81. doi:, 10.1107/S1399004713031040. Epub 2014 Jan 31. PMID:24531491<ref>PMID:24531491</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> [[http://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.	+

-	~~==About this Structure==~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4m0w]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA]~~.	+	== References ==
-		+	<references/>
-	==~~Reference~~==	+	__TOC__
-	<references ~~group="xtra"~~/><~~references~~/>	+	</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
		+	[[Category: Cvhsa]]
	[[Category: Chen, H Y.]]		[[Category: Chen, H Y.]]
	[[Category: Cheng, S C.]]		[[Category: Cheng, S C.]]

OCA at 05:20, 13 February 2014

2014-02-13T05:20:42Z

←Older revision		Revision as of 05:20, 13 February 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4m0w\| PDB=4m0w \| SCENE= }}
		+	===Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin===

-	The ~~entry 4m0w~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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> [[http://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.

-	~~Authors~~: ~~Chou, C~~.Y.~~, Chen, H~~.Y.~~, Lai, H~~.~~Y., Cheng, S~~.C.~~, Chou, Y~~.W.	+	==About this Structure==
		+	[[4m0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0W OCA].

-	~~Description~~: ~~Crystal Structure of SARS~~-~~CoV papain~~-like protease ~~C112S mutant in complex with~~ ubiquitin	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Bos taurus]]
		+	[[Category: Chen, H Y.]]
		+	[[Category: Cheng, S C.]]
		+	[[Category: Chou, C Y.]]
		+	[[Category: Chou, Y W.]]
		+	[[Category: Lai, H Y.]]
		+	[[Category: Hydrolase-protein binding complex]]
		+	[[Category: Papain-like protease-ubiquitin complex]]
		+	[[Category: Protein hydrolase and deubiquitination]]

OCA at 07:53, 21 August 2013

2013-08-21T07:53:53Z

←Older revision		Revision as of 07:53, 21 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4m0w is ON HOLD	+	The entry 4m0w is ON HOLD until Paper Publication

	Authors: Chou, C.Y., Chen, H.Y., Lai, H.Y., Cheng, S.C., Chou, Y.W.		Authors: Chou, C.Y., Chen, H.Y., Lai, H.Y., Cheng, S.C., Chou, Y.W.

	Description: Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin		Description: Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin

OCA: Protected "4m0w" [edit=sysop:move=sysop]

2013-08-14T07:21:16Z

Protected "4m0w" [edit=sysop:move=sysop]

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Revision as of 07:21, 14 August 2013