2zu4 - Revision history

OCA at 13:54, 1 November 2023

2023-11-01T13:54:47Z

←Older revision		Revision as of 13:54, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='2zu4' size='340' side='right'caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='2zu4' size='340' side='right'caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</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]] 1.93Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [~~http~~://pdbe.org/2zu4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2zu4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu4 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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [https://pdbe.org/2zu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [https://www.ebi.ac.uk/pdbsum/2zu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu4 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/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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	==See Also==		==See Also==
-	*[[~~SARS Coronavirus Main Proteinase~~\|~~SARS Coronavirus Main Proteinase~~]]	+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Cvhsa]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hsu, M F~~]]	+	[[Category: Severe acute respiratory syndrome-related coronavirus]]
-	[[Category: ~~Lee, C C~~]]	+	[[Category: Hsu MF]]
-	[[Category: ~~Wang, A H.J~~]]	+	[[Category: Lee CC]]
-	[[Category: ~~Hydrolase]]~~	+	[[Category: Wang AH-J]]
-	~~[[Category: Hydrolase~~-~~hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Protease-inhibitor complex~~]]	+

OCA at 12:10, 29 July 2020

2020-07-29T12:10:02Z

←Older revision		Revision as of 12:10, 29 July 2020
Line 1:		Line 1:

	==Complex structure of SARS-CoV 3CL protease with TG-0204998==		==Complex structure of SARS-CoV 3CL protease with TG-0204998==
-	<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>	+	<StructureSection load='2zu4' size='340' side='right'caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://pdbe.org/2zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu4 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://pdbe.org/2zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	</StructureSection>		</StructureSection>
	[[Category: Cvhsa]]		[[Category: Cvhsa]]
		+	[[Category: Large Structures]]
	[[Category: Hsu, M F]]		[[Category: Hsu, M F]]
	[[Category: Lee, C C]]		[[Category: Lee, C C]]

OCA at 07:08, 18 October 2018

2018-10-18T07:08:24Z

←Older revision		Revision as of 07:08, 18 October 2018
Line 1:		Line 1:
		+
	==Complex structure of SARS-CoV 3CL protease with TG-0204998==		==Complex structure of SARS-CoV 3CL protease with TG-0204998==
	<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://pdbe.org/2zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://pdbe.org/2zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zu4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/2zu4_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/2zu4_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>

OCA at 11:19, 8 February 2016

2016-02-08T11:19:06Z

←Older revision		Revision as of 11:19, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://pdbe.org/2zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 17:
	<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=2zu4 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 27:
	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 2zu4" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Sars coronavirus~~]]	+	[[Category: Cvhsa]]
	[[Category: Hsu, M F]]		[[Category: Hsu, M F]]
	[[Category: Lee, C C]]		[[Category: Lee, C C]]

OCA at 22:56, 24 December 2014

2014-12-24T22:56:33Z

←Older revision		Revision as of 22:56, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
-	[[Category: Hsu, M F.]]	+	[[Category: Hsu, M F]]
-	[[Category: Lee, C C.]]	+	[[Category: Lee, C C]]
-	[[Category: Wang, A H.J.]]	+	[[Category: Wang, A H.J]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Protease-inhibitor complex]]		[[Category: Protease-inhibitor complex]]

OCA at 07:43, 29 September 2014

2014-09-29T07:43:17Z

←Older revision		Revision as of 07:43, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2zu4.~~png~~\|~~left~~\|200px]]	+	==Complex structure of SARS-CoV 3CL protease with TG-0204998==
		+	<StructureSection load='2zu4' size='340' side='right' caption='[[2zu4]], [[Resolution\|resolution]] 1.93Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2zu4]] is a 1 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=2ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZU4 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZU3:N-[(BENZYLOXY)CARBONYL]-3-[(2,2-DIMETHYLPROPANOYL)AMINO]-L-ALANYL-N-[(1R)-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}PENTYL]-L-LEUCINAMIDE'>ZU3</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ztx\|2ztx]], [[2zty\|2zty]], [[2ztz\|2ztz]], [[2zu1\|2zu1]], [[2zu2\|2zu2]], [[2zu3\|2zu3]], [[2zu5\|2zu5]]</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=2zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zu4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zu4 PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/2zu4_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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human coxsackievirus (CV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. In picornavirus, a chymotrypsin-like protease (3C(pro)) is required for viral replication by processing the polyproteins, and thus it is regarded as an antiviral drug target. A 3C-like protease (3CL(pro)) also exists in human coronaviruses (CoV) such as 229E and the one causing severe acute respiratory syndrome (SARS). To combat SARS, we previously had developed peptidomimetic and zinc-coordinating inhibitors of 3CL(pro). As shown in the present study, some of these compounds were also found to be active against 3C(pro) of CV strain B3 (CVB3). Several crystal structures of 3C(pro) from CVB3 and 3CL(pro) from CoV-229E and SARS-CoV in complex with the inhibitors were solved. The zinc-coordinating inhibitor is tetrahedrally coordinated to the His(40)-Cys(147) catalytic dyad of CVB3 3C(pro). The presence of specific binding pockets for the residues of peptidomimetic inhibitors explains the binding specificity. Our results provide a structural basis for inhibitor optimization and development of potential drugs for antiviral therapies.

-	~~{{STRUCTURE_2zu4\| PDB=2zu4 \| SCENE= }}~~	+	Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds.,Lee CC, Kuo CJ, Ko TP, Hsu MF, Tsui YC, Chang SC, Yang S, Chen SJ, Chen HC, Hsu MC, Shih SR, Liang PH, Wang AH J Biol Chem. 2009 Mar 20;284(12):7646-55. Epub 2009 Jan 14. PMID:19144641<ref>PMID:19144641</ref>

-	~~===Complex structure~~ of ~~SARS-CoV 3CL protease with TG-0204998===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19144641}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2zu4]] is a 1 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=2ZU4 OCA].~~	+

	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:019144641<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Hsu, M F.]]		[[Category: Hsu, M F.]]

OCA at 09:58, 20 October 2012

2012-10-20T09:58:19Z

←Older revision		Revision as of 09:58, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2zu4]] is a 1 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=2ZU4 OCA].	+	[[2zu4]] is a 1 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=2ZU4 OCA].

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

OCA: Protected "2zu4" [edit=sysop:move=sysop]

2012-07-26T00:34:06Z

Protected "2zu4" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:34, 26 July 2012

OCA at 00:34, 26 July 2012

2012-07-26T00:34:04Z

←Older revision		Revision as of 00:34, 26 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2zu4.png\|left\|200px]]		[[Image:2zu4.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2zu4", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2zu4\| PDB=2zu4 \| SCENE= }}		{{STRUCTURE_2zu4\| PDB=2zu4 \| SCENE= }}

	===Complex structure of SARS-CoV 3CL protease with TG-0204998===		===Complex structure of SARS-CoV 3CL protease with TG-0204998===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19144641}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19144641 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19144641}}		{{ABSTRACT_PUBMED_19144641}}

	==About this Structure==		==About this Structure==
-	~~2ZU4~~ is a 1 chain structure of 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=2ZU4 OCA].	+	[[2zu4]] is a 1 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=2ZU4 OCA].
		+
		+	==See Also==
		+	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19144641~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019144641</ref><references group="xtra"/>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Hsu, M F.]]		[[Category: Hsu, M F.]]
Line 29:		Line 20:
	[[Category: Wang, A H.J.]]		[[Category: Wang, A H.J.]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Protease-inhibitor complex]]		[[Category: Protease-inhibitor complex]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 2 15:27:32 2009''

OCA at 12:27, 2 April 2009

2009-04-02T12:27:33Z

←Older revision		Revision as of 12:27, 2 April 2009
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:2zu4.~~jpg~~\|left\|200px]]	+	[[Image:2zu4.png\|left\|200px]]

	<!--		<!--
Line 12:		Line 12:
	===Complex structure of SARS-CoV 3CL protease with TG-0204998===		===Complex structure of SARS-CoV 3CL protease with TG-0204998===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19144641}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19144641 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19144641}}

	==About this Structure==		==About this Structure==
	2ZU4 is a 1 chain structure of 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=2ZU4 OCA].		2ZU4 is a 1 chain structure of 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=2ZU4 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19144641</ref><references group="xtra"/>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Hsu, M F.]]		[[Category: Hsu, M F.]]
Line 23:		Line 32:
	[[Category: Protease-inhibitor complex]]		[[Category: Protease-inhibitor complex]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 14 13~~:29:46 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 2 15:27:32 2009''