5ref - Revision history

OCA at 13:19, 18 February 2026

2026-02-18T13:19:02Z

← Older revision		Revision as of 13:19, 18 February 2026
Line 3:		Line 3:
	<StructureSection load='5ref' size='340' side='right'caption='[[5ref]], [[Resolution\|resolution]] 1.61Å' scene=''>		<StructureSection load='5ref' size='340' side='right'caption='[[5ref]], [[Resolution\|resolution]] 1.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[5ref]] 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=5REF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.61Å</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]] 1.61Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [https://pdbe.org/5ref PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [https://www.ebi.ac.uk/pdbsum/5ref PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref 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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [https://pdbe.org/5ref PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [https://www.ebi.ac.uk/pdbsum/5ref PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></td></tr>
	</table>		</table>
	== ~~Function~~ ==		<div style="background-color:#fffaf0;">
	[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]		== Publication Abstract from PubMed ==
			COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.

			Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease.,Douangamath A, Fearon D, Gehrtz P, Krojer T, Lukacik P, Owen CD, Resnick E, Strain-Damerell C, Aimon A, Abranyi-Balogh P, Brandao-Neto J, Carbery A, Davison G, Dias A, Downes TD, Dunnett L, Fairhead M, Firth JD, Jones SP, Keeley A, Keseru GM, Klein HF, Martin MP, Noble MEM, O'Brien P, Powell A, Reddi RN, Skyner R, Snee M, Waring MJ, Wild C, London N, von Delft F, Walsh MA Nat Commun. 2020 Oct 7;11(1):5047. doi: 10.1038/s41467-020-18709-w. PMID:33028810<ref>PMID:33028810</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5ref" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 18:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Severe acute respiratory syndrome coronavirus 2]]~~
	[[Category: Aimon A]]		[[Category: Aimon A]]
	[[Category: Brandao-Neto J]]		[[Category: Brandao-Neto J]]

OCA at 13:44, 1 March 2024

2024-03-01T13:44:44Z

← Older revision		Revision as of 13:44, 1 March 2024
Line 1:		Line 1:

	==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z24758179==		==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z24758179==
	<StructureSection load='5ref' size='340' side='right'caption='[[5ref]]' scene=''>		<StructureSection load='5ref' size='340' side='right'caption='[[5ref]], [[Resolution\|resolution]] 1.61Å' 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=5REF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ref]] 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=5REF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REF 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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [https://pdbe.org/5ref PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [https://www.ebi.ac.uk/pdbsum/5ref PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.61Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [https://pdbe.org/5ref PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [https://www.ebi.ac.uk/pdbsum/5ref PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref 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]

	==See Also==		==See Also==
	*[[Virus protease 3D structures\|Virus protease 3D structures]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
			[[Category: Severe acute respiratory syndrome coronavirus 2]]
	[[Category: Aimon A]]		[[Category: Aimon A]]
	[[Category: Brandao-Neto J]]		[[Category: Brandao-Neto J]]

OCA at 06:42, 24 February 2021

2021-02-24T06:42:29Z

← Older revision		Revision as of 06:42, 24 February 2021
Line 1:		Line 1:

	==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z24758179==		==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z24758179==
	<StructureSection load='5ref' size='340' side='right'caption='[[5ref]]~~, [[Resolution\|resolution]] 1.61Å~~' scene=''>		<StructureSection load='5ref' size='340' side='right'caption='[[5ref]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[5ref]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Wcpv Wcpv].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [https://pdbe.org/5ref PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [https://www.ebi.ac.uk/pdbsum/5ref PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></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=2697049 WCPV])</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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [~~http~~://pdbe.org/5ref PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ref PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></td></tr>
	</table>		</table>
	== ~~Function~~ ==
	[[http://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]		==See Also==
	~~== References ==~~		*[[Virus protease 3D structures\|Virus protease 3D structures]]
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Wcpv]]~~		[[Category: Aimon A]]
	[[Category: Aimon, A]]		[[Category: Brandao-Neto J]]
	[[Category: Brandao-Neto, J]]		[[Category: Carbery A]]
	[[Category: Carbery, A]]		[[Category: Douangamath A]]
	~~[[Category: Delft, F von~~]]		[[Category: Dunnett L]]
	[[Category: Douangamath, A]]		[[Category: Fearon D]]
	[[Category: Dunnett, L]]		[[Category: Gehrtz P]]
	[[Category: Fearon, D]]		[[Category: Krojer T]]
	[[Category: Gehrtz, P]]		[[Category: London N]]
	[[Category: Krojer, T]]		[[Category: Lukacik P]]
	[[Category: London, N]]		[[Category: Owen CD]]
	[[Category: Lukacik, P]]		[[Category: Powell AJ]]
	[[Category: Owen~~, C D~~]]		[[Category: Resnick E]]
	[[Category: Powell~~, A J~~]]		[[Category: Skyner R]]
	[[Category: Resnick, E]]		[[Category: Snee M]]
	[[Category: Skyner, R]]		[[Category: Strain-Damerell CM]]
	[[Category: Snee, M]]		[[Category: Walsh MA]]
	[[Category: Strain-Damerell~~, C M~~]]		[[Category: Wild C]]
	[[Category: Walsh~~, M A~~]]		[[Category: Von Delft F]]
	[[Category: Wild, C]]
	[[Category: ~~Hydrolase-hydrolase inhibitor complex]]~~
	~~[[Category: Pandda]]~~
	~~[[Category: Sgc - diamond i04-1 fragment screening]]~~
	~~[[Category: Xchemexplorer~~]]

OCA at 06:13, 6 May 2020

2020-05-06T06:13:03Z

← Older revision		Revision as of 06:13, 6 May 2020
Line 5:		Line 5:
	<table><tr><td colspan='2'>[[5ref]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Wcpv Wcpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ref]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Wcpv Wcpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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=2697049 WCPV])</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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [http://pdbe.org/5ref PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [http://www.ebi.ac.uk/pdbsum/5ref PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref 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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [http://pdbe.org/5ref PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [http://www.ebi.ac.uk/pdbsum/5ref PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://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]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:08, 8 April 2020

2020-04-08T07:08:38Z

← Older revision		Revision as of 07:08, 8 April 2020
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	<StructureSection load='5ref' size='340' side='right'caption='[[5ref]], [[Resolution\|resolution]] 1.61Å' scene=''>		<StructureSection load='5ref' size='340' side='right'caption='[[5ref]], [[Resolution\|resolution]] 1.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ref]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5REF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ref]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Wcpv Wcpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5REF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SU:METHYL+3-(METHYLSULFONYLAMINO)BENZOATE'>6SU</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [http://pdbe.org/5ref PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [http://www.ebi.ac.uk/pdbsum/5ref PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref 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=5ref FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ref OCA], [http://pdbe.org/5ref PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ref RCSB], [http://www.ebi.ac.uk/pdbsum/5ref PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ref ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
			[[Category: Wcpv]]
	[[Category: Aimon, A]]		[[Category: Aimon, A]]
	[[Category: Brandao-Neto, J]]		[[Category: Brandao-Neto, J]]

OCA: Protected "5ref" [edit=sysop:move=sysop]

2020-03-27T09:55:25Z

Protected "5ref" [edit=sysop:move=sysop]

← Older revision	Revision as of 09:55, 27 March 2020
(No difference)

OCA: New page: ==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z24758179==