7rfw - Revision history

OCA at 15:41, 22 December 2021

OCA — Wed, 22 Dec 2021 15:41:54 GMT

←Older revision		Revision as of 15:41, 22 December 2021
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7rfw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFW FirstGlance]. <br>		<table><tr><td colspan='2'>[[7rfw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WI:(1R,2S,5S)-N-{(2S)-1-~~amino~~-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide'>4WI</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4WI:(1R,2S,5S)-N-{(1E,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide'>4WI</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='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=7rfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfw OCA], [https://pdbe.org/7rfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfw RCSB], [https://www.ebi.ac.uk/pdbsum/7rfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfw 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=7rfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfw OCA], [https://pdbe.org/7rfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfw RCSB], [https://www.ebi.ac.uk/pdbsum/7rfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfw ProSAT]</span></td></tr>

OCA at 14:18, 17 November 2021

OCA — Wed, 17 Nov 2021 14:18:31 GMT

←Older revision		Revision as of 14:18, 17 November 2021
Line 1:		Line 1:

	==Structure of SARS-CoV-2 main protease in complex with a covalent inhibitor==		==Structure of SARS-CoV-2 main protease in complex with a covalent inhibitor==
-	<StructureSection load='7rfw' size='340' side='right'caption='[[7rfw]]' scene=''>	+	<StructureSection load='7rfw' size='340' side='right'caption='[[7rfw]], [[Resolution\|resolution]] 1.73Å' 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=7RFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rfw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFW 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=7rfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfw OCA], [https://pdbe.org/7rfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfw RCSB], [https://www.ebi.ac.uk/pdbsum/7rfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfw 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=4WI:(1R,2S,5S)-N-{(2S)-1-amino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide'>4WI</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=7rfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfw OCA], [https://pdbe.org/7rfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfw RCSB], [https://www.ebi.ac.uk/pdbsum/7rfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfw 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 ==
		+	[Figure: see text].
		+
		+	An oral SARS-CoV-2 M(pro) inhibitor clinical candidate for the treatment of COVID-19.,Owen DR, Allerton CMN, Anderson AS, Aschenbrenner L, Avery M, Berritt S, Boras B, Cardin RD, Carlo A, Coffman KJ, Dantonio A, Di L, Eng H, Ferre R, Gajiwala KS, Gibson SA, Greasley SE, Hurst BL, Kadar EP, Kalgutkar AS, Lee JC, Lee J, Liu W, Mason SW, Noell S, Novak JJ, Obach RS, Ogilvie K, Patel NC, Pettersson M, Rai DK, Reese MR, Sammons MF, Sathish JG, Singh RSP, Steppan CM, Stewart AE, Tuttle JB, Updyke L, Verhoest PR, Wei L, Yang Q, Zhu Y Science. 2021 Nov 2:eabl4784. doi: 10.1126/science.abl4784. PMID:34726479<ref>PMID:34726479</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rfw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ferre RA]]	+	[[Category: SARS coronavirus main proteinase]]
-	[[Category: Greasley SE]]	+	[[Category: Ferre, R A]]
-	[[Category: Liu W]]	+	[[Category: Greasley, S E]]
-	[[Category: Stewart AE]]	+	[[Category: Liu, W]]
		+	[[Category: Stewart, A E]]
		+	[[Category: Hydrolase-inhibitor complex]]
		+	[[Category: Protease sars-cov-2 covalent complex inhibitor]]

OCA at 06:16, 10 November 2021

OCA — Wed, 10 Nov 2021 06:16:49 GMT

←Older revision		Revision as of 06:16, 10 November 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7rfw is ~~ON HOLD until Paper Publication~~	+	==Structure of SARS-CoV-2 main protease in complex with a covalent inhibitor==
-		+	<StructureSection load='7rfw' size='340' side='right'caption='[[7rfw]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFW FirstGlance]. <br>
-	~~Description~~:	+	</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=7rfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfw OCA], [https://pdbe.org/7rfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfw RCSB], [https://www.ebi.ac.uk/pdbsum/7rfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfw ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ferre RA]]
		+	[[Category: Greasley SE]]
		+	[[Category: Liu W]]
		+	[[Category: Stewart AE]]

OCA at 09:34, 28 July 2021

OCA — Wed, 28 Jul 2021 09:34:51 GMT

←Older revision		Revision as of 09:34, 28 July 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7rfw is ON HOLD	+	The entry 7rfw is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 21 Jul 2021 08:03:54 GMT

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

←Older revision

Revision as of 08:03, 21 July 2021

OCA: New page: '''Unreleased structure''' The entry 7rfw is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 21 Jul 2021 08:03:53 GMT

New page: '''Unreleased structure''' The entry 7rfw is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7rfw is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]