OCA at 05:33, 14 May 2025

2025-05-14T05:33:46Z

← Older revision		Revision as of 05:33, 14 May 2025
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	~~'''Unreleased structure'''~~

	~~The entry~~ 9bs8 is ~~ON HOLD until 2026~~-05-13		==Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107==
			<StructureSection load='9bs8' size='340' side='right'caption='[[9bs8]], [[Resolution\|resolution]] 1.70Å' scene=''>
	~~Authors~~: ~~Blankenship~~, L.R., ~~Liu~~, W.R.		== Structural highlights ==
			<table><tr><td colspan='2'>[[9bs8]] 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=9BS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BS8 FirstGlance]. <br>
	~~Description~~: ~~Structure~~ of the ~~SARS~~-~~CoV~~-2 ~~main protease~~ in ~~complex~~ with ~~inhibitor YR~~-B-~~107~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AR4:(phenylmethyl)+(7~{S})-7-[[(2~{S})-1-oxidanyl-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]carbamoyl]-6-azaspiro[3.4]octane-6-carboxylate'>A1AR4</scene></td></tr>
	[[Category: Blankenship~~, L.R~~]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9bs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bs8 OCA], [https://pdbe.org/9bs8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bs8 RCSB], [https://www.ebi.ac.uk/pdbsum/9bs8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bs8 ProSAT]</span></td></tr>
	[[Category: Liu~~, W.R~~]]		</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]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Severe acute respiratory syndrome coronavirus 2]]
			[[Category: Blankenship LR]]
			[[Category: Liu WR]]

OCA at 04:46, 19 June 2024

2024-06-19T04:46:49Z

← Older revision		Revision as of 04:46, 19 June 2024
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 9bs8 is ON HOLD		The entry 9bs8 is ON HOLD until 2026-05-13

	Authors: Blankenship, L.R., Liu, W.R.		Authors: Blankenship, L.R., Liu, W.R.
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	Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107		Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Blankenship, L.R]]
	[[Category: Liu, W.R]]		[[Category: Liu, W.R]]
	~~[[Category: Blankenship, L.R]]~~

OCA at 15:02, 29 May 2024

2024-05-29T15:02:41Z

← Older revision		Revision as of 15:02, 29 May 2024
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	Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107		Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Liu, W.R]]
	[[Category: Blankenship, L.R]]		[[Category: Blankenship, L.R]]
	~~[[Category: Liu, W.R]]~~

OCA: Protected "9bs8" [edit=sysop:move=sysop]

2024-05-22T07:05:05Z

Protected "9bs8" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:05, 22 May 2024
(No difference)

OCA: New page: '''Unreleased structure''' The entry 9bs8 is ON HOLD Authors: Blankenship, L.R., Liu, W.R. Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107 [[C...

2024-05-22T07:05:04Z

New page: '''Unreleased structure''' The entry 9bs8 is ON HOLD Authors: Blankenship, L.R., Liu, W.R. Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107 [[C...

New page

'''Unreleased structure'''

The entry 9bs8 is ON HOLD

Authors: Blankenship, L.R., Liu, W.R.

Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107
[[Category: Unreleased Structures]]
[[Category: Blankenship, L.R]]
[[Category: Liu, W.R]]

9bs8 - Revision history

OCA at 05:33, 14 May 2025

OCA at 04:46, 19 June 2024

OCA at 15:02, 29 May 2024

OCA: Protected "9bs8" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 9bs8 is ON HOLD Authors: Blankenship, L.R., Liu, W.R. Description: Structure of the SARS-CoV-2 main protease in complex with inhibitor YR-B-107 [[C...