OCA at 17:16, 18 October 2023

OCA — Wed, 18 Oct 2023 17:16:49 GMT

←Older revision		Revision as of 17:16, 18 October 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7ujg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Room-temperature X-ray structure of monomeric SARS-CoV-2 main protease catalytic domain (MPro1-196) in complex with GC-376==
		+	<StructureSection load='7ujg' size='340' side='right'caption='[[7ujg]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7ujg]] 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=7UJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UJG 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]] 1.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K36:(1S,2S)-2-({N-[(BENZYLOXY)CARBONYL]-L-LEUCYL}AMINO)-1-HYDROXY-3-[(3S)-2-OXOPYRROLIDIN-3-YL]PROPANE-1-SULFONIC+ACID'>K36</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=7ujg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ujg OCA], [https://pdbe.org/7ujg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ujg RCSB], [https://www.ebi.ac.uk/pdbsum/7ujg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ujg ProSAT]</span></td></tr>
		+	</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 ==
		+	The monomeric catalytic domain (residues 1-199) of SARS-CoV-2 main protease (MPro(1-199)) fused to 25 amino acids of its flanking nsp4 region mediates its autoprocessing at the nsp4-MPro(1-199) junction. We report the catalytic activity and the dissociation constants of MPro(1-199) and its analogs with the covalent inhibitors GC373 and nirmatrelvir (NMV), and the estimated monomer-dimer equilibrium constants of these complexes. Mass spectrometry indicates the presence of the accumulated adduct of NMV bound to MPro(WT) and MPro(1-199) and not of GC373. A room temperature crystal structure reveals a native-like fold of the catalytic domain with an unwound oxyanion loop (E state). In contrast, the structure of a covalent complex of the catalytic domain-GC373 or NMV shows an oxyanion loop conformation (E* state) resembling the full-length mature dimer. These results suggest that the E-E* equilibrium modulates autoprocessing of the main protease when converting from a monomeric polyprotein precursor to the mature dimer.

-	~~Authors: Kovalevsky, A~~., Kneller~~, D.W.~~, Coates, L.	+	Autoprocessing and oxyanion loop reorganization upon GC373 and nirmatrelvir binding of monomeric SARS-CoV-2 main protease catalytic domain.,Nashed NT, Kneller DW, Coates L, Ghirlando R, Aniana A, Kovalevsky A, Louis JM Commun Biol. 2022 Sep 16;5(1):976. doi: 10.1038/s42003-022-03910-y. PMID:36114420<ref>PMID:36114420</ref>

-	~~Description: Room-temperature X-ray structure~~ of ~~monomeric SARS~~-~~CoV~~-~~2 main protease catalytic domain (MPro1-196) in complex with GC-376~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Kneller, D.W~~]]	+	<div class="pdbe-citations 7ujg" style="background-color:#fffaf0;"></div>
-	[[Category: Coates, L]]	+	== References ==
-	[[Category: Kovalevsky, A]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Coates L]]
		+	[[Category: Kneller DW]]
		+	[[Category: Kovalevsky A]]

OCA at 08:33, 13 April 2022

OCA — Wed, 13 Apr 2022 08:33:53 GMT

←Older revision		Revision as of 08:33, 13 April 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Kovalevsky, A., Kneller, D.W., Coates, L.		Authors: Kovalevsky, A., Kneller, D.W., Coates, L.

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

OCA — Wed, 06 Apr 2022 09:07:31 GMT

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

←Older revision

Revision as of 09:07, 6 April 2022

OCA: New page: '''Unreleased structure''' The entry 7ujg is ON HOLD Authors: Kovalevsky, A., Kneller, D.W., Coates, L. Description: Room-temperature X-ray structure of monomeric SARS-CoV-2 main prote...

OCA — Wed, 06 Apr 2022 09:07:30 GMT

New page: '''Unreleased structure''' The entry 7ujg is ON HOLD Authors: Kovalevsky, A., Kneller, D.W., Coates, L. Description: Room-temperature X-ray structure of monomeric SARS-CoV-2 main prote...

New page

'''Unreleased structure'''

The entry 7ujg is ON HOLD

Authors: Kovalevsky, A., Kneller, D.W., Coates, L.

Description: Room-temperature X-ray structure of monomeric SARS-CoV-2 main protease catalytic domain (MPro1-196) in complex with GC-376
[[Category: Unreleased Structures]]
[[Category: Kneller, D.W]]
[[Category: Coates, L]]
[[Category: Kovalevsky, A]]

7ujg - Revision history

OCA at 17:16, 18 October 2023

OCA at 08:33, 13 April 2022

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

OCA: New page: '''Unreleased structure''' The entry 7ujg is ON HOLD Authors: Kovalevsky, A., Kneller, D.W., Coates, L. Description: Room-temperature X-ray structure of monomeric SARS-CoV-2 main prote...