7wym - Revision history

OCA at 17:46, 29 November 2023

2023-11-29T17:46:09Z

←Older revision		Revision as of 17:46, 29 November 2023
Line 3:		Line 3:
	<StructureSection load='7wym' size='340' side='right'caption='[[7wym]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='7wym' size='340' side='right'caption='[[7wym]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7wym]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WYM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7wym]] is a 1 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=7WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WYM FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=G7L:N-methyl-N~~-[[~~4-(trifluoromethyl)-1,3-thiazol-2-yl~~]~~methyl~~]~~prop-~~2~~-enamide'>G7L</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]] 2.05Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G7L:N-methyl-N-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]methyl]prop-2-enamide'>G7L</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=7wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wym OCA], [https://pdbe.org/7wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wym RCSB], [https://www.ebi.ac.uk/pdbsum/7wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wym 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=7wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wym OCA], [https://pdbe.org/7wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wym RCSB], [https://www.ebi.ac.uk/pdbsum/7wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wym ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~R1A_SARS2 R1A_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]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7] 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]	+	[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 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~SARS~~ coronavirus ~~main proteinase~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: Cui, S]]	+	[[Category: Cui S]]
-	[[Category: Gao, X]]	+	[[Category: Gao X]]
-	[[Category: Hou, P]]	+	[[Category: Hou P]]
-	[[Category: Qin, B]]	+	[[Category: Qin B]]
-	~~[[Category: Structure of the sars-cov-2 main protease with 337 inhibitor]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 07:35, 29 June 2022

2022-06-29T07:35:53Z

←Older revision		Revision as of 07:35, 29 June 2022
Line 1:		Line 1:

	==Structure of the SARS-COV-2 main protease with 337 inhibitor==		==Structure of the SARS-COV-2 main protease with 337 inhibitor==
-	<StructureSection load='7wym' size='340' side='right'caption='[[7wym]]' scene=''>	+	<StructureSection load='7wym' size='340' side='right'caption='[[7wym]], [[Resolution\|resolution]] 2.05Å' 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=7WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WYM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7wym]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WYM 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=7wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wym OCA], [https://pdbe.org/7wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wym RCSB], [https://www.ebi.ac.uk/pdbsum/7wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wym 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=G7L:N-methyl-N-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]methyl]prop-2-enamide'>G7L</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=7wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wym OCA], [https://pdbe.org/7wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wym RCSB], [https://www.ebi.ac.uk/pdbsum/7wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wym ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/R1A_SARS2 R1A_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]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7] 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]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C(pro)) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M(pro)) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M(pro) to inhibit its activity. We demonstrate that targeting the active site cysteine of M(pro) can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.
		+
		+	Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 main protease.,Qin B, Craven GB, Hou P, Chesti J, Lu X, Child ES, Morgan RML, Niu W, Zhao L, Armstrong A, Mann DJ, Cui S Acta Pharm Sin B. 2022 Jun 9. pii: S2211-3835(22)00268-4. doi:, 10.1016/j.apsb.2022.06.002. PMID:35702321<ref>PMID:35702321</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7wym" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cui S]]	+	[[Category: SARS coronavirus main proteinase]]
-	[[Category: Gao X]]	+	[[Category: Cui, S]]
-	[[Category: Hou P]]	+	[[Category: Gao, X]]
-	[[Category: Qin B]]	+	[[Category: Hou, P]]
		+	[[Category: Qin, B]]
		+	[[Category: Structure of the sars-cov-2 main protease with 337 inhibitor]]
		+	[[Category: Viral protein]]

OCA at 09:47, 22 June 2022

2022-06-22T09:47:37Z

←Older revision		Revision as of 09:47, 22 June 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7wym ~~is ON HOLD~~	+	==Structure of the SARS-COV-2 main protease with 337 inhibitor==
-		+	<StructureSection load='7wym' size='340' side='right'caption='[[7wym]]' scene=''>
-	~~Authors~~: ~~Qin~~, B., ~~Hou~~, P.~~, Gao, X~~., ~~Cui~~, S.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WYM FirstGlance]. <br>
-	~~Description: Structure of the SARS-COV-2 main protease with 337 inhibitor~~	+	</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=7wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wym OCA], [https://pdbe.org/7wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wym RCSB], [https://www.ebi.ac.uk/pdbsum/7wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wym ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Hou, P~~]]	+	__TOC__
-	[[Category: Gao, X]]	+	</StructureSection>
-	[[Category: ~~Cui, S~~]]	+	[[Category: Large Structures]]
-	[[Category: Qin, B]]	+	[[Category: Cui S]]
		+	[[Category: Gao X]]
		+	[[Category: Hou P]]
		+	[[Category: Qin B]]

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

2022-02-23T06:43:20Z

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

←Older revision

Revision as of 06:43, 23 February 2022

OCA: New page: '''Unreleased structure''' The entry 7wym is ON HOLD Authors: Qin, B., Hou, P., Gao, X., Cui, S. Description: Structure of the SARS-COV-2 main protease with 337 inhibitor [[Category: U...

2022-02-23T06:43:19Z

New page: '''Unreleased structure''' The entry 7wym is ON HOLD Authors: Qin, B., Hou, P., Gao, X., Cui, S. Description: Structure of the SARS-COV-2 main protease with 337 inhibitor [[Category: U...

New page

'''Unreleased structure'''

The entry 7wym is ON HOLD

Authors: Qin, B., Hou, P., Gao, X., Cui, S.

Description: Structure of the SARS-COV-2 main protease with 337 inhibitor
[[Category: Unreleased Structures]]
[[Category: Hou, P]]
[[Category: Gao, X]]
[[Category: Cui, S]]
[[Category: Qin, B]]