OCA at 11:48, 13 December 2023

2023-12-13T11:48:44Z

←Older revision		Revision as of 11:48, 13 December 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8uh5 is ~~ON HOLD~~	+	==Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-272==
-		+	<StructureSection load='8uh5' size='340' side='right'caption='[[8uh5]], [[Resolution\|resolution]] 1.74Å' scene=''>
-	~~Authors~~: ~~Bulut~~, H., ~~Hayashi~~, H., ~~Kuwata~~, N., ~~Tsuji~~, K., ~~Das~~, D., ~~Tamamura~~, H., ~~Mitsuya~~, H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8uh5]] 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=8UH5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UH5 FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~SARS~~-~~CoV~~-2 ~~main protease~~ in ~~complex~~ with an ~~inhibitor TKB~~-~~272~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.74Å</td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=WOK:(1R,2S,5S)-N-{(1S,2S)-1-(5-fluoro-1,3-benzothiazol-2-yl)-1-hydroxy-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'>WOK</scene></td></tr>
-	[[Category: ~~Hayashi, H~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8uh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uh5 OCA], [https://pdbe.org/8uh5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uh5 RCSB], [https://www.ebi.ac.uk/pdbsum/8uh5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uh5 ProSAT]</span></td></tr>
-	[[Category: Bulut, H]]	+	</table>
-	[[Category: ~~Tamamura,~~ H]]	+	== Function ==
-	[[Category: Kuwata, N]]	+	[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]
-	[[Category: ~~Tsuji, K~~]]	+	== References ==
-	[[Category: ~~Mitsuya,~~ H]]	+	<references/>
-	[[Category: ~~Das, D~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Bulut H]]
		+	[[Category: Das D]]
		+	[[Category: Hayashi H]]
		+	[[Category: Kuwata N]]
		+	[[Category: Mitsuya H]]
		+	[[Category: Tamamura H]]
		+	[[Category: Tsuji K]]

OCA: Protected "8uh5" [edit=sysop:move=sysop]

2023-10-18T12:27:45Z

Protected "8uh5" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:27, 18 October 2023

OCA: New page: '''Unreleased structure''' The entry 8uh5 is ON HOLD Authors: Bulut, H., Hayashi, H., Kuwata, N., Tsuji, K., Das, D., Tamamura, H., Mitsuya, H. Description: Crystal structure of SARS-C...

2023-10-18T12:27:42Z

New page: '''Unreleased structure''' The entry 8uh5 is ON HOLD Authors: Bulut, H., Hayashi, H., Kuwata, N., Tsuji, K., Das, D., Tamamura, H., Mitsuya, H. Description: Crystal structure of SARS-C...

New page

'''Unreleased structure'''

The entry 8uh5 is ON HOLD

Authors: Bulut, H., Hayashi, H., Kuwata, N., Tsuji, K., Das, D., Tamamura, H., Mitsuya, H.

Description: Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-272
[[Category: Unreleased Structures]]
[[Category: Hayashi, H]]
[[Category: Bulut, H]]
[[Category: Tamamura, H]]
[[Category: Kuwata, N]]
[[Category: Tsuji, K]]
[[Category: Mitsuya, H]]
[[Category: Das, D]]

8uh5 - Revision history

OCA at 11:48, 13 December 2023

OCA: Protected "8uh5" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8uh5 is ON HOLD Authors: Bulut, H., Hayashi, H., Kuwata, N., Tsuji, K., Das, D., Tamamura, H., Mitsuya, H. Description: Crystal structure of SARS-C...