2duc - Revision history

OCA at 08:30, 25 October 2023

2023-10-25T08:30:16Z

← Older revision		Revision as of 08:30, 25 October 2023
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	<StructureSection load='2duc' size='340' side='right'caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='2duc' size='340' side='right'caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [https://pdbe.org/2duc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [https://www.ebi.ac.uk/pdbsum/2duc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2duc ProSAT], [https://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></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]] 1.7Å</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [https://pdbe.org/2duc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [https://www.ebi.ac.uk/pdbsum/2duc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2duc ProSAT], [https://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/~~R1AB_CVHSA R1AB_CVHSA~~]~~] The replicase polyprotein of coronaviruses is a multifunctional~~ protein~~: it contains the activities necessary for~~ the transcription of ~~negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as~~ proteinases responsible for the cleavage of the ~~polyprotein into functional products~~ (~~By similarity~~).<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~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> ~~The helicase which contains~~ a ~~zinc finger structure displays RNA and DNA duplex-unwinding activities~~ with ~~5' to 3' polarity. Its ATPase activity is strongly stimulated by poly~~(U)~~, poly(dT), poly(C), poly(dA), but not~~ by ~~poly(G)~~. ~~Activity of helicase is dependent on magnesium~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~The exoribonuclease acts on~~ both ~~ssRNA and dsRNA in a~~ 3' to 5' ~~direction~~.<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> ~~NendoU is a~~ Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> ~~<ref>PMID:19369340</ref>~~		[https://www.uniprot.org/uniprot/R1AB_SARS R1AB_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> Responsible for replication and transcription of the viral RNA genome.<ref>PMID:22791111</ref> Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.<ref>PMID:12917423</ref> <ref>PMID:22615777</ref> Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585).<ref>PMID:16549795</ref> <ref>PMID:20421945</ref> <ref>PMID:21593585</ref> <ref>PMID:22635272</ref> <ref>PMID:23966862</ref> <ref>PMID:29511076</ref> Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.<ref>PMID:18417574</ref> <ref>PMID:20421945</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Kim, Y T~~]]		[[Category: Severe acute respiratory syndrome-related coronavirus]]
	[[Category: ~~Muramatsu, T~~]]		[[Category: Kim YT]]
	[[Category: ~~Structural genomic~~]]		[[Category: Muramatsu T]]
	[[Category: Shirouzu, M]]		[[Category: Shirouzu M]]
	[[Category: Takemoto, C]]		[[Category: Takemoto C]]
	[[Category: Wang, H]]		[[Category: Wang H]]
	[[Category: Yokoyama, S]]		[[Category: Yokoyama S]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: National project on protein structural and functional analyse]]~~
	~~[[Category: Nppsfa]]~~
	~~[[Category: Rsgi]]~~
	~~[[Category: Sars coronavirus main proteinase~~]]

OCA at 10:01, 26 May 2021

2021-05-26T10:01:21Z

← Older revision		Revision as of 10:01, 26 May 2021
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	<StructureSection load='2duc' size='340' side='right'caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='2duc' size='340' side='right'caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [~~http~~://pdbe.org/2duc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2duc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2duc ProSAT], [~~http~~://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [https://pdbe.org/2duc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [https://www.ebi.ac.uk/pdbsum/2duc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2duc ProSAT], [https://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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> The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<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> NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>		[[https://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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> The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<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> NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
	*[[~~SARS Coronavirus Main Proteinase~~\|~~SARS Coronavirus Main Proteinase~~]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:52, 21 August 2019

2019-08-21T07:52:58Z

← Older revision		Revision as of 07:52, 21 August 2019
Line 1:		Line 1:

	==Crystal structure of SARS coronavirus main proteinase(3CLPRO)==		==Crystal structure of SARS coronavirus main proteinase(3CLPRO)==
	<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='2duc' size='340' side='right'caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
Line 12:		Line 12:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/du/2duc_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/du/2duc_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 27:		Line 27:
	</div>		</div>
	<div class="pdbe-citations 2duc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2duc" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Kim, Y T]]		[[Category: Kim, Y T]]
	[[Category: Muramatsu, T]]		[[Category: Muramatsu, T]]

OCA at 00:29, 16 November 2017

2017-11-16T00:29:19Z

← Older revision		Revision as of 00:29, 16 November 2017
Line 27:		Line 27:
	</div>		</div>
	<div class="pdbe-citations 2duc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2duc" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:08, 17 August 2017

2017-08-17T06:08:07Z

← Older revision		Revision as of 06:08, 17 August 2017
Line 1:		Line 1:

	==Crystal structure of SARS coronavirus main proteinase(3CLPRO)==		==Crystal structure of SARS coronavirus main proteinase(3CLPRO)==
	<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://pdbe.org/2duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>		</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://pdbe.org/2duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2duc ProSAT], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2duc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) cleaves 11 sites in the polyproteins, including its own N- and C-terminal autoprocessing sites, by recognizing P4-P1 and P1'. In this study, we determined the crystal structure of 3CLpro with the C-terminal prosequence and the catalytic-site C145A mutation, in which the enzyme binds the C-terminal prosequence of another molecule. Surprisingly, Phe at the P3' position [Phe(P3')] is snugly accommodated in the S3' pocket. Mutations of Phe(P3') impaired the C-terminal autoprocessing, but did not affect N-terminal autoprocessing. This difference was ascribed to the P2 residue, Phe(P2) and Leu(P2), in the C- and N-terminal sites, as follows. The S3' subsite is formed by Phe(P2)-induced conformational changes of 3CLpro and the direct involvement of Phe(P2) itself. In contrast, the N-terminal prosequence with Leu(P2) does not cause such conformational changes for the S3' subsite formation. In fact, the mutation of Phe(P2) to Leu in the C-terminal autoprocessing site abolishes the dependence on Phe(P3'). These mechanisms explain why Phe is required at the P3' position when the P2 position is occupied by Phe rather than Leu, which reveals a type of subsite cooperativity. Moreover, the peptide consisting of P4-P1 with Leu(P2) inhibits protease activity, whereas that with Phe(P2) exhibits a much smaller inhibitory effect, because Phe(P3') is missing. Thus, this subsite cooperativity likely exists to avoid the autoinhibition of the enzyme by its mature C-terminal sequence, and to retain the efficient C-terminal autoprocessing by the use of Phe(P2).

			SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity.,Muramatsu T, Takemoto C, Kim YT, Wang H, Nishii W, Terada T, Shirouzu M, Yokoyama S Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):12997-13002. Epub 2016 Oct 31. PMID:27799534<ref>PMID:27799534</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 2duc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 34:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Cvhsa]]~~
	[[Category: Kim, Y T]]		[[Category: Kim, Y T]]
	[[Category: Muramatsu, T]]		[[Category: Muramatsu, T]]

OCA at 16:29, 11 September 2015

2015-09-11T16:29:21Z

← Older revision		Revision as of 16:29, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>		</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://pdbe.org/2duc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Sars coronavirus~~]]		[[Category: Cvhsa]]
	[[Category: Kim, Y T]]		[[Category: Kim, Y T]]
	[[Category: Muramatsu, T]]		[[Category: Muramatsu, T]]

OCA at 19:01, 25 December 2014

2014-12-25T19:01:14Z

← Older revision		Revision as of 19:01, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>		</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 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> The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<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> NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 18:		Line 20:
	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Kim, Y T.]]		[[Category: Kim, Y T]]
	[[Category: Muramatsu, T.]]		[[Category: Muramatsu, T]]
	[[Category: ~~RSGI, RIKEN~~ Structural ~~Genomics/Proteomics Initiative.~~]]		[[Category: Structural genomic]]
	[[Category: Shirouzu, M.]]		[[Category: Shirouzu, M]]
	[[Category: Takemoto, C.]]		[[Category: Takemoto, C]]
	[[Category: Wang, H.]]		[[Category: Wang, H]]
	[[Category: Yokoyama, S.]]		[[Category: Yokoyama, S]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: National project on protein structural and functional analyse]]		[[Category: National project on protein structural and functional analyse]]
	[[Category: Nppsfa]]		[[Category: Nppsfa]]
	~~[[Category: Riken structural genomics/proteomics initiative]]~~
	[[Category: Rsgi]]		[[Category: Rsgi]]
	[[Category: Sars coronavirus main proteinase]]		[[Category: Sars coronavirus main proteinase]]
	~~[[Category: Structural genomic]]~~

OCA at 10:34, 29 September 2014

2014-09-29T10:34:28Z

← Older revision		Revision as of 10:34, 29 September 2014
Line 1:		Line 1:
	~~[[Image:2duc.png\|left\|200px]]~~		==Crystal structure of SARS coronavirus main proteinase(3CLPRO)==
			<StructureSection load='2duc' size='340' side='right' caption='[[2duc]], [[Resolution\|resolution]] 1.70Å' scene=''>
	~~{{STRUCTURE_2duc\| PDB=2duc \| SCENE= }}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2duc]] 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=2DUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DUC FirstGlance]. <br>
	===Crystal structure of SARS coronavirus main proteinase(3CLPRO)===		</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=2duc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2duc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2duc RCSB], [http://www.ebi.ac.uk/pdbsum/2duc PDBsum], [http://www.topsan.org/Proteins/RSGI/2duc TOPSAN]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
	==~~About this Structure~~==		[[Image:Consurf_key_small.gif\|200px\|right]]
	[[2duc]] 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=2DUC OCA].		Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/du/2duc_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>

	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
			__TOC__
			</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Kim, Y T.]]		[[Category: Kim, Y T.]]

OCA at 20:18, 20 October 2012

2012-10-20T20:18:06Z

← Older revision		Revision as of 20:18, 20 October 2012
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
	[[2duc]] is a 2 chain structure ~~of [[SARS Coronavirus Main Proteinase]]~~ 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=2DUC OCA].		[[2duc]] 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=2DUC OCA].

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

OCA: Protected "2duc" [edit=sysop:move=sysop]

2012-07-27T10:02:28Z

Protected "2duc" [edit=sysop:move=sysop]

← Older revision	Revision as of 10:02, 27 July 2012
(No difference)