4twy - Revision history

OCA at 15:18, 8 November 2023

OCA — Wed, 08 Nov 2023 15:18:24 GMT

←Older revision		Revision as of 15:18, 8 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4twy]] 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=4TWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TWY FirstGlance]. <br>		<table><tr><td colspan='2'>[[4twy]] 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=4TWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TWY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [https://pdbe.org/4twy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [https://www.ebi.ac.uk/pdbsum/4twy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy 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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [https://pdbe.org/4twy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [https://www.ebi.ac.uk/pdbsum/4twy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:50, 22 March 2023

OCA — Wed, 22 Mar 2023 07:50:02 GMT

←Older revision		Revision as of 07:50, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='4twy' size='340' side='right'caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4twy' size='340' side='right'caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4twy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4TWY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4twy]] 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=4TWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TWY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [https://pdbe.org/4twy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [https://www.ebi.ac.uk/pdbsum/4twy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [~~http~~://pdbe.org/4twy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4twy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</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_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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]	+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
-	*[[Virus protease\|Virus protease]]	+
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~SARS~~ coronavirus ~~main proteinase~~]]	+	[[Category: Severe acute respiratory syndrome-related coronavirus]]
-	[[Category: Akaji, K]]	+	[[Category: Akaji K]]
-	[[Category: Nakagawa, A]]	+	[[Category: Nakagawa A]]
-	[[Category: Sanjho, A]]	+	[[Category: Sanjho A]]
-	[[Category: Shimamoto, Y]]	+	[[Category: Shimamoto Y]]
-	[[Category: Teruya, K]]	+	[[Category: Teruya K]]
-	[[Category: Yamashita, E]]	+	[[Category: Yamashita E]]
-	~~[[Category: Designed inhibitor]]~~	+
-	~~[[Category: Hydrase proteinase converting]]~~	+
-	~~[[Category: Hydrase-inhibitor complex]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 15:57, 29 January 2020

OCA — Wed, 29 Jan 2020 15:57:21 GMT

←Older revision		Revision as of 15:57, 29 January 2020
Line 3:		Line 3:
	<StructureSection load='4twy' size='340' side='right'caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4twy' size='340' side='right'caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4twy]] 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=4TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TWY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4twy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TWY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://pdbe.org/4twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy 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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://pdbe.org/4twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</span></td></tr>
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Cvhsa]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: SARS coronavirus main proteinase]]		[[Category: SARS coronavirus main proteinase]]

OCA at 15:05, 10 May 2019

OCA — Fri, 10 May 2019 15:05:16 GMT

←Older revision		Revision as of 15:05, 10 May 2019
Line 1:		Line 1:

	==Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor==		==Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor==
-	<StructureSection load='4twy' size='340' side='right' caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4twy' size='340' side='right'caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4twy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TWY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4twy]] 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=4TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TWY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://pdbe.org/4twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy 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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://pdbe.org/4twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4twy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4twy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
		+	*[[Virus protease\|Virus protease]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Cvhsa]]
		+	[[Category: Large Structures]]
	[[Category: SARS coronavirus main proteinase]]		[[Category: SARS coronavirus main proteinase]]
	[[Category: Akaji, K]]		[[Category: Akaji, K]]

OCA at 01:21, 19 January 2017

OCA — Thu, 19 Jan 2017 01:21:02 GMT

←Older revision		Revision as of 01:21, 19 January 2017
Line 1:		Line 1:
		+
	==Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor==		==Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor==
	<StructureSection load='4twy' size='340' side='right' caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4twy' size='340' side='right' caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy 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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://pdbe.org/4twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4twy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4twy" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:58, 18 February 2015

OCA — Wed, 18 Feb 2015 12:58:55 GMT

←Older revision		Revision as of 12:58, 18 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor==
		+	<StructureSection load='4twy' size='340' side='right' caption='[[4twy]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4twy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TWY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3BL:(2S)-2-({[(3S,4AR,8AS)-2-(BIPHENYL-4-YLCARBONYL)DECAHYDROISOQUINOLIN-3-YL]METHYL}AMINO)-3-(1H-IMIDAZOL-5-YL)PROPANAL'>3BL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4tww\|4tww]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.69 3.4.22.69] </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=4twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4twy RCSB], [http://www.ebi.ac.uk/pdbsum/4twy PDBsum]</span></td></tr>
		+	</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The design and evaluation of a novel decahydroisoquinolin scaffold as an inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL(pro)) are described. Focusing on hydrophobic interactions at the S2 site, the decahydroisoquinolin scaffold was designed by connecting the P2 site cyclohexyl group of the substrate-based inhibitor to the main-chain at the alpha-nitrogen atom of the P2 position via a methylene linker. Starting from a cyclohexene enantiomer obtained by salt resolution, trans-decahydroisoquinolin derivatives were synthesized. All decahydroisoquinolin inhibitors synthesized showed moderate but clear inhibitory activities for SARS 3CL(pro), which confirmed the fused ring structure of the decahydroisoquinolin functions as a novel scaffold for SARS 3CL(pro) inhibitor. X-ray crystallographic analyses of the SARS 3CL(pro) in a complex with the decahydroisoquinolin inhibitor revealed the expected interactions at the S1 and S2 sites, as well as additional interactions at the N-substituent of the inhibitor.

-	~~The entry 4twy is ON HOLD until Paper Publication~~	+	Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors.,Shimamoto Y, Hattori Y, Kobayashi K, Teruya K, Sanjoh A, Nakagawa A, Yamashita E, Akaji K Bioorg Med Chem. 2015 Feb 15;23(4):876-90. doi: 10.1016/j.bmc.2014.12.028. Epub, 2014 Dec 20. PMID:25614110<ref>PMID:25614110</ref>

-	~~Authors: Akaji~~, K.~~, Teruya, K~~.~~, Shimamoto, Y., Sanjho, A., Yamashita, E., Nakagawa, A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Teruya~~, K]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: SARS coronavirus main proteinase]]
		+	[[Category: Akaji, K]]
	[[Category: Nakagawa, A]]		[[Category: Nakagawa, A]]
-	[[Category: Akaji, K]]
-	[[Category: Yamashita, E]]
	[[Category: Sanjho, A]]		[[Category: Sanjho, A]]
	[[Category: Shimamoto, Y]]		[[Category: Shimamoto, Y]]
		+	[[Category: Teruya, K]]
		+	[[Category: Yamashita, E]]
		+	[[Category: Designed inhibitor]]
		+	[[Category: Hydrase proteinase converting]]
		+	[[Category: Hydrase-inhibitor complex]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 17:55, 24 December 2014

OCA — Wed, 24 Dec 2014 17:55:52 GMT

←Older revision		Revision as of 17:55, 24 December 2014
Line 6:		Line 6:

	Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor		Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor
		+	[[Category: Unreleased Structures]]
		+	[[Category: Teruya, K]]
		+	[[Category: Nakagawa, A]]
		+	[[Category: Akaji, K]]
		+	[[Category: Yamashita, E]]
		+	[[Category: Sanjho, A]]
		+	[[Category: Shimamoto, Y]]

OCA at 01:22, 7 August 2014

OCA — Thu, 07 Aug 2014 01:22:44 GMT

←Older revision		Revision as of 01:22, 7 August 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

-	Authors: Akaji, K., Teruya, K., Shimamoto,Y., Sanjho, A., Yamashita, E., Nakagawa, A.	+	Authors: Akaji, K., Teruya, K., Shimamoto, Y., Sanjho, A., Yamashita, E., Nakagawa, A.

	Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor		Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor

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

OCA — Wed, 09 Jul 2014 07:00:49 GMT

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

←Older revision

Revision as of 07:00, 9 July 2014

OCA: New page: '''Unreleased structure''' The entry 4twy is ON HOLD Authors: Akaji, K., Teruya, K., Shimamoto,Y., Sanjho, A., Yamashita, E., Nakagawa, A. Description: Structure of SARS-3CL protease c...

OCA — Wed, 09 Jul 2014 07:00:48 GMT

New page: '''Unreleased structure''' The entry 4twy is ON HOLD Authors: Akaji, K., Teruya, K., Shimamoto,Y., Sanjho, A., Yamashita, E., Nakagawa, A. Description: Structure of SARS-3CL protease c...

New page

'''Unreleased structure'''

The entry 4twy is ON HOLD

Authors: Akaji, K., Teruya, K., Shimamoto,Y., Sanjho, A., Yamashita, E., Nakagawa, A.

Description: Structure of SARS-3CL protease complex with a phenylbenzoyl (S,R)-N-decalin type inhibitor