7lkr - Revision history

OCA at 15:52, 18 October 2023

OCA — Wed, 18 Oct 2023 15:52:53 GMT

←Older revision		Revision as of 15:52, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='7lkr' size='340' side='right'caption='[[7lkr]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='7lkr' size='340' side='right'caption='[[7lkr]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lkr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~2019-ncov 2019-ncov~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lkr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=Y4D:(1R,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y4D</scene>, <scene name='pdbligand=Y5S:(1S,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y5S</scene>, <scene name='pdbligand=Y8Y:(1R,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y8Y</scene>, <scene name='pdbligand=Y91:(1S,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y91</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]] 1.65Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=Y4D:(1R,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y4D</scene>, <scene name='pdbligand=Y5S:(1S,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y5S</scene>, <scene name='pdbligand=Y8Y:(1R,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y8Y</scene>, <scene name='pdbligand=Y91:(1S,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y91</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkr OCA], [https://pdbe.org/7lkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkr RCSB], [https://www.ebi.ac.uk/pdbsum/7lkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkr 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=7lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkr OCA], [https://pdbe.org/7lkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkr RCSB], [https://www.ebi.ac.uk/pdbsum/7lkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7]	+	[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: SARS coronavirus main proteinase]]
-	[[Category: Baird, M A]]
-	[[Category: Battaile, K P]]
-	[[Category: Chamandi, S D]]
-	[[Category: Chang, K O]]
-	[[Category: Groutas, W C]]
-	[[Category: Kashipathy, M M]]
-	[[Category: Kim, Y]]
-	[[Category: Lovell, S]]
-	[[Category: Nguyen, H N]]
-	[[Category: Rathnayake, A D]]
-	[[Category: Shadipeni, N]]
-	[[Category: Covid-19]]
-	[[Category: Hydrolase-inhibitor complex]]
-	[[Category: Protease]]
-	[[Category: Sars-cov-2 3cl protease inhhibitor]]
	[[Category: Severe acute respiratory syndrome coronavirus 2]]		[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Baird MA]]
		+	[[Category: Battaile KP]]
		+	[[Category: Chamandi SD]]
		+	[[Category: Chang KO]]
		+	[[Category: Groutas WC]]
		+	[[Category: Kashipathy MM]]
		+	[[Category: Kim Y]]
		+	[[Category: Lovell S]]
		+	[[Category: Nguyen HN]]
		+	[[Category: Rathnayake AD]]
		+	[[Category: Shadipeni N]]

OCA at 10:11, 14 July 2021

OCA — Wed, 14 Jul 2021 10:11:22 GMT

←Older revision		Revision as of 10:11, 14 July 2021
Line 1:		Line 1:

	==1.65 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 2a==		==1.65 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 2a==
-	<StructureSection load='7lkr' size='340' side='right'caption='[[7lkr]]' scene=''>	+	<StructureSection load='7lkr' size='340' side='right'caption='[[7lkr]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lkr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKR 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=7lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkr OCA], [https://pdbe.org/7lkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkr RCSB], [https://www.ebi.ac.uk/pdbsum/7lkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkr ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=Y4D:(1R,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y4D</scene>, <scene name='pdbligand=Y5S:(1S,2S)-2-((S)-2-(((((1R,3s,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y5S</scene>, <scene name='pdbligand=Y8Y:(1R,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y8Y</scene>, <scene name='pdbligand=Y91:(1S,2S)-2-((S)-2-(((((1R,3r,5S)-bicyclo[3.3.1]nonan-3-yl)methoxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-((S)-2-oxopyrrolidin-3-yl)propane-1-sulfonic+acid'>Y91</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/SARS_coronavirus_main_proteinase SARS coronavirus main proteinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkr OCA], [https://pdbe.org/7lkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkr RCSB], [https://www.ebi.ac.uk/pdbsum/7lkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkr ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7] 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. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 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.[UniProtKB:P0C6X7]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A series of nondeuterated and deuterated dipeptidyl aldehyde and masked aldehyde inhibitors that incorporate in their structure a conformationally constrained cyclohexane moiety was synthesized and found to potently inhibit severe acute respiratory syndrome coronavirus-2 3CL protease in biochemical and cell-based assays. Several of the inhibitors were also found to be nanomolar inhibitors of Middle East respiratory syndrome coronavirus 3CL protease. The corresponding latent aldehyde bisulfite adducts were found to be equipotent to the precursor aldehydes. High-resolution cocrystal structures confirmed the mechanism of action and illuminated the structural determinants involved in binding. The spatial disposition of the compounds disclosed herein provides an effective means of accessing new chemical space and optimizing pharmacological activity. The cellular permeability of the identified inhibitors and lack of cytotoxicity warrant their advancement as potential therapeutics for COVID-19.
		+
		+	Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease.,Dampalla CS, Kim Y, Bickmeier N, Rathnayake AD, Nguyen HN, Zheng J, Kashipathy MM, Baird MA, Battaile KP, Lovell S, Perlman S, Chang KO, Groutas WC J Med Chem. 2021 Jul 2. doi: 10.1021/acs.jmedchem.1c00319. PMID:34213885<ref>PMID:34213885</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lkr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Baird MA]]	+	[[Category: SARS coronavirus main proteinase]]
-	[[Category: Battaile KP]]	+	[[Category: Baird, M A]]
-	[[Category: Chamandi SD]]	+	[[Category: Battaile, K P]]
-	[[Category: Chang KO]]	+	[[Category: Chamandi, S D]]
-	[[Category: Groutas WC]]	+	[[Category: Chang, K O]]
-	[[Category: Kashipathy MM]]	+	[[Category: Groutas, W C]]
-	[[Category: Kim Y]]	+	[[Category: Kashipathy, M M]]
-	[[Category: Lovell S]]	+	[[Category: Kim, Y]]
-	[[Category: Nguyen HN]]	+	[[Category: Lovell, S]]
-	[[Category: Rathnayake AD]]	+	[[Category: Nguyen, H N]]
-	[[Category: Shadipeni N]]	+	[[Category: Rathnayake, A D]]
		+	[[Category: Shadipeni, N]]
		+	[[Category: Covid-19]]
		+	[[Category: Hydrolase-inhibitor complex]]
		+	[[Category: Protease]]
		+	[[Category: Sars-cov-2 3cl protease inhhibitor]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]

OCA at 10:02, 17 February 2021

OCA — Wed, 17 Feb 2021 10:02:45 GMT

←Older revision		Revision as of 10:02, 17 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7lkr ~~is ON HOLD~~	+	==1.65 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 2a==
-		+	<StructureSection load='7lkr' size='340' side='right'caption='[[7lkr]]' scene=''>
-	~~Authors~~: ~~Lovell, S~~.~~, Kashipathy, M~~.M.~~, Battaile, K~~.P.~~, Chamandi, S~~.D.~~, Rathnayake, A~~.D., ~~Nguyen, H~~.N., ~~Baird~~, M.A.~~, Kim, Y~~., ~~Shadipeni, N~~.~~, Chang, K~~.O., ~~Groutas, W~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKR FirstGlance]. <br>
-	~~Description: 1.65 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 2a~~	+	</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=7lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkr OCA], [https://pdbe.org/7lkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkr RCSB], [https://www.ebi.ac.uk/pdbsum/7lkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkr ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Battaile, K.P~~]]	+	__TOC__
-	[[Category: ~~Chamandi, S.D~~]]	+	</StructureSection>
-	[[Category: ~~Lovell, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Baird, M.A~~]]	+	[[Category: Baird MA]]
-	[[Category: ~~Nguyen, H.N~~]]	+	[[Category: Battaile KP]]
-	[[Category: ~~Groutas, W.C~~]]	+	[[Category: Chamandi SD]]
-	[[Category: ~~Chang, K.O~~]]	+	[[Category: Chang KO]]
-	[[Category: ~~Kashipathy, M.M~~]]	+	[[Category: Groutas WC]]
-	[[Category: ~~Kim, Y~~]]	+	[[Category: Kashipathy MM]]
-	[[Category: Rathnayake~~, A.D~~]]	+	[[Category: Kim Y]]
-	[[Category: Shadipeni, N]]	+	[[Category: Lovell S]]
		+	[[Category: Nguyen HN]]
		+	[[Category: Rathnayake AD]]
		+	[[Category: Shadipeni N]]

OCA: Protected "7lkr" [edit=sysop:move=sysop]

OCA — Wed, 10 Feb 2021 09:19:56 GMT

Protected "7lkr" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:19, 10 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lkr is ON HOLD Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Chamandi, S.D., Rathnayake, A.D., Nguyen, H.N., Baird, M.A., Kim, Y., Shadipe...

OCA — Wed, 10 Feb 2021 09:19:55 GMT

New page: '''Unreleased structure''' The entry 7lkr is ON HOLD Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Chamandi, S.D., Rathnayake, A.D., Nguyen, H.N., Baird, M.A., Kim, Y., Shadipe...

New page

'''Unreleased structure'''

The entry 7lkr is ON HOLD

Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Chamandi, S.D., Rathnayake, A.D., Nguyen, H.N., Baird, M.A., Kim, Y., Shadipeni, N., Chang, K.O., Groutas, W.C.

Description: 1.65 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 2a
[[Category: Unreleased Structures]]
[[Category: Battaile, K.P]]
[[Category: Chamandi, S.D]]
[[Category: Lovell, S]]
[[Category: Baird, M.A]]
[[Category: Nguyen, H.N]]
[[Category: Groutas, W.C]]
[[Category: Chang, K.O]]
[[Category: Kashipathy, M.M]]
[[Category: Kim, Y]]
[[Category: Rathnayake, A.D]]
[[Category: Shadipeni, N]]