OCA at 16:11, 18 October 2023

OCA — Wed, 18 Oct 2023 16:11:08 GMT

←Older revision		Revision as of 16:11, 18 October 2023
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-	====	+	==SARS-CoV-2 main protease in complex with N-terminal autoprocessing substrate==
-	<StructureSection load='7mgs' size='340' side='right'caption='[[7mgs]]' scene=''>	+	<StructureSection load='7mgs' size='340' side='right'caption='[[7mgs]], [[Resolution\|resolution]] 1.84Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7mgs]] 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=7MGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MGS 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=7mgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mgs OCA], [https://pdbe.org/7mgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mgs RCSB], [https://www.ebi.ac.uk/pdbsum/7mgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mgs 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]] 1.84Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7mgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mgs OCA], [https://pdbe.org/7mgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mgs RCSB], [https://www.ebi.ac.uk/pdbsum/7mgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mgs 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 ==
		+	The main protease (M(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), is an ideal target for pharmaceutical inhibition. M(pro) is conserved among coronaviruses and distinct from human proteases. Viral replication depends on the cleavage of the viral polyprotein at multiple sites. We present crystal structures of SARS-CoV-2 M(pro) bound to two viral substrate peptides. The structures show how M(pro) recognizes distinct substrates and how subtle changes in substrate accommodation can drive large changes in catalytic efficiency. One peptide, constituting the junction between viral nonstructural proteins 8 and 9 (nsp8/9), has P1' and P2' residues that are unique among the SARS-CoV-2 M(pro) cleavage sites but conserved among homologous junctions in coronaviruses. M(pro) cleaves nsp8/9 inefficiently, and amino acid substitutions at P1' or P2' can enhance catalysis. Visualization of M(pro) with intact substrates provides new templates for antiviral drug design and suggests that the coronavirus lifecycle selects for finely tuned substrate-dependent catalytic parameters.
		+
		+	Recognition of Divergent Viral Substrates by the SARS-CoV-2 Main Protease.,MacDonald EA, Frey G, Namchuk MN, Harrison SC, Hinshaw SM, Windsor IW ACS Infect Dis. 2021 Sep 10;7(9):2591-2595. doi: 10.1021/acsinfecdis.1c00237. , Epub 2021 Aug 26. PMID:34437808<ref>PMID:34437808</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7mgs" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Hinshaw SM]]
		+	[[Category: MacDonald EA]]
		+	[[Category: Windsor IW]]

OCA at 07:33, 25 June 2021

OCA — Fri, 25 Jun 2021 07:33:10 GMT

←Older revision		Revision as of 07:33, 25 June 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7mgs ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7mgs' size='340' side='right'caption='[[7mgs]]' scene=''>
-	~~Authors~~: ~~MacDonald, E~~.A.~~, Windsor, I~~.W.~~, Hinshaw, S~~.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~SARS-CoV-2 main protease in complex with N-terminal autoprocessing substrate~~	+	</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=7mgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mgs OCA], [https://pdbe.org/7mgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mgs RCSB], [https://www.ebi.ac.uk/pdbsum/7mgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mgs ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Macdonald~~, E.A]]	+	__TOC__
-	[[Category: ~~Windsor, I.W~~]]	+	</StructureSection>
-	[[Category: ~~Hinshaw, S.M~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

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

OCA — Wed, 21 Apr 2021 06:23:54 GMT

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

←Older revision

Revision as of 06:23, 21 April 2021

OCA: New page: '''Unreleased structure''' The entry 7mgs is ON HOLD Authors: MacDonald, E.A., Windsor, I.W., Hinshaw, S.M. Description: SARS-CoV-2 main protease in complex with N-terminal autoprocess...

OCA — Wed, 21 Apr 2021 06:23:53 GMT

New page: '''Unreleased structure''' The entry 7mgs is ON HOLD Authors: MacDonald, E.A., Windsor, I.W., Hinshaw, S.M. Description: SARS-CoV-2 main protease in complex with N-terminal autoprocess...

New page

'''Unreleased structure'''

The entry 7mgs is ON HOLD

Authors: MacDonald, E.A., Windsor, I.W., Hinshaw, S.M.

Description: SARS-CoV-2 main protease in complex with N-terminal autoprocessing substrate
[[Category: Unreleased Structures]]
[[Category: Macdonald, E.A]]
[[Category: Windsor, I.W]]
[[Category: Hinshaw, S.M]]

7mgs - Revision history

OCA at 16:11, 18 October 2023

OCA at 07:33, 25 June 2021

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

OCA: New page: '''Unreleased structure''' The entry 7mgs is ON HOLD Authors: MacDonald, E.A., Windsor, I.W., Hinshaw, S.M. Description: SARS-CoV-2 main protease in complex with N-terminal autoprocess...