OCA at 10:55, 15 November 2023

OCA — Wed, 15 Nov 2023 10:55:14 GMT

←Older revision		Revision as of 10:55, 15 November 2023
Line 1:		Line 1:

-	====	+	==The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease==
-	<StructureSection load='7d3c' size='340' side='right'caption='[[7d3c]]' scene=''>	+	<StructureSection load='7d3c' size='340' side='right'caption='[[7d3c]], [[Resolution\|resolution]] 2.20Å' 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'>[[7d3c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D3C 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=7d3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d3c OCA], [https://pdbe.org/7d3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d3c RCSB], [https://www.ebi.ac.uk/pdbsum/7d3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d3c 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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=010:PHENYLMETHANOL'>010</scene>, <scene name='pdbligand=02J:5-METHYL-1,2-OXAZOLE-3-CARBOXYLIC+ACID'>02J</scene>, <scene name='pdbligand=PJE:(E,4S)-4-AZANYL-5-[(3S)-2-OXIDANYLIDENEPYRROLIDIN-3-YL]PENT-2-ENOIC+ACID'>PJE</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=7d3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d3c OCA], [https://pdbe.org/7d3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d3c RCSB], [https://www.ebi.ac.uk/pdbsum/7d3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d3c ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/R1AB_MERS1 R1AB_MERS1] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Promotes the degradation of host mRNAs by inducing an endonucleolytic RNA cleavage in template mRNAs, and inhibits of host mRNA translation, a function that is separable from its RNA cleavage activity. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.<ref>PMID:26311885</ref> 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]<ref>PMID:25142582</ref> 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][PROSITE-ProRule:PRU00772] 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.[UniProtKB:P0C6X7] Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity).[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__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z-~~disk~~]]	+	[[Category: Middle East respiratory syndrome-related coronavirus]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Ren Z]]
		+	[[Category: Yan L]]

OCA at 14:28, 3 November 2021

OCA — Wed, 03 Nov 2021 14:28:03 GMT

←Older revision		Revision as of 14:28, 3 November 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7d3c ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7d3c' size='340' side='right'caption='[[7d3c]]' scene=''>
-	~~Authors~~: ~~Yan, L~~.~~, Ren, Z~~.	+	== 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~~: ~~The newly emerged SARS-like coronavirus HCoV-EMC also has an~~ "~~Achilles' heel~~": ~~current effective inhibitor targeting a 3C~~-~~like protease~~	+	</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=7d3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d3c OCA], [https://pdbe.org/7d3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d3c RCSB], [https://www.ebi.ac.uk/pdbsum/7d3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d3c ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Yan, L~~]]	+	__TOC__
-	[[Category: ~~Ren,~~ Z]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7d3c" [edit=sysop:move=sysop]

OCA — Wed, 23 Sep 2020 09:01:59 GMT

Protected "7d3c" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:01, 23 September 2020

OCA: New page: '''Unreleased structure''' The entry 7d3c is ON HOLD Authors: Yan, L., Ren, Z. Description: The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effec...

OCA — Wed, 23 Sep 2020 09:01:57 GMT

New page: '''Unreleased structure''' The entry 7d3c is ON HOLD Authors: Yan, L., Ren, Z. Description: The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effec...

New page

'''Unreleased structure'''

The entry 7d3c is ON HOLD

Authors: Yan, L., Ren, Z.

Description: The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease
[[Category: Unreleased Structures]]
[[Category: Yan, L]]
[[Category: Ren, Z]]

7d3c - Revision history

OCA at 10:55, 15 November 2023

OCA at 14:28, 3 November 2021

OCA: Protected "7d3c" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7d3c is ON HOLD Authors: Yan, L., Ren, Z. Description: The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effec...