OCA at 17:24, 29 November 2023

2023-11-29T17:24:28Z

←Older revision		Revision as of 17:24, 29 November 2023
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-	====	+	==the complex of SARS-CoV2 3cl and NB2B4==
-	<StructureSection load='7vfb' size='340' side='right'caption='[[7vfb]]' scene=''>	+	<StructureSection load='7vfb' size='340' side='right'caption='[[7vfb]], [[Resolution\|resolution]] 2.00Å' 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'>[[7vfb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_bactrianus Camelus bactrianus] and [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=7VFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VFB 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=7vfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vfb OCA], [https://pdbe.org/7vfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vfb RCSB], [https://www.ebi.ac.uk/pdbsum/7vfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vfb 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]] 2Å</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=7vfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vfb OCA], [https://pdbe.org/7vfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vfb RCSB], [https://www.ebi.ac.uk/pdbsum/7vfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vfb 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 ==
		+	SignificanceThe coronavirus main protease (M(pro)) is required for viral replication. Here, we obtained the extended conformation of the native monomer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M(pro) by trapping it with nanobodies and found that the catalytic domain and the helix domain dissociate, revealing allosteric targets. Another monomeric state is termed compact conformation and is similar to one protomer of the dimeric form. We designed a Nanoluc Binary Techonology (NanoBiT)-based high-throughput allosteric inhibitor assay based on structural conformational change. Our results provide insight into the maturation, dimerization, and catalysis of the coronavirus M(pro) and pave a way to develop an anticoronaviral drug through targeting the maturation process to inhibit the autocleavage of M(pro).
		+
		+	An extended conformation of SARS-CoV-2 main protease reveals allosteric targets.,Sun Z, Wang L, Li X, Fan C, Xu J, Shi Z, Qiao H, Lan Z, Zhang X, Li L, Zhou X, Geng Y Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2120913119. doi: , 10.1073/pnas.2120913119. Epub 2022 Mar 24. PMID:35324337<ref>PMID:35324337</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7vfb" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Camelus bactrianus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Geng Y]]
		+	[[Category: Sun ZC]]
		+	[[Category: Wang L]]

OCA at 10:48, 30 March 2022

2022-03-30T10:48:57Z

←Older revision		Revision as of 10:48, 30 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7vfb ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7vfb' size='340' side='right'caption='[[7vfb]]' scene=''>
-	~~Authors~~: ~~Geng, Y~~.~~, Sun, Z~~.C.~~, Wang, L~~.	+	== 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 ~~complex of SARS-CoV2 3cl and NB2B4~~	+	</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=7vfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vfb OCA], [https://pdbe.org/7vfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vfb RCSB], [https://www.ebi.ac.uk/pdbsum/7vfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vfb ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Sun, Z~~.C]]	+	__TOC__
-	[[Category: ~~Wang, L~~]]	+	</StructureSection>
-	[[Category: ~~Geng, Y~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 12:20, 29 December 2021

2021-12-29T12:20:16Z

←Older revision		Revision as of 12:20, 29 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Geng, Y., Sun, Z.C., Wang, L.		Authors: Geng, Y., Sun, Z.C., Wang, L.

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

2021-09-22T05:43:49Z

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

←Older revision

Revision as of 05:43, 22 September 2021

OCA: New page: '''Unreleased structure''' The entry 7vfb is ON HOLD Authors: Geng, Y., Sun, Z.C., Wang, L. Description: the complex of SARS-CoV2 3cl and NB2B4 Category: Unreleased Structures [[Ca...

2021-09-22T05:43:48Z

New page: '''Unreleased structure''' The entry 7vfb is ON HOLD Authors: Geng, Y., Sun, Z.C., Wang, L. Description: the complex of SARS-CoV2 3cl and NB2B4 Category: Unreleased Structures [[Ca...

New page

'''Unreleased structure'''

The entry 7vfb is ON HOLD

Authors: Geng, Y., Sun, Z.C., Wang, L.

Description: the complex of SARS-CoV2 3cl and NB2B4
[[Category: Unreleased Structures]]
[[Category: Sun, Z.C]]
[[Category: Wang, L]]
[[Category: Geng, Y]]

7vfb - Revision history

OCA at 17:24, 29 November 2023

OCA at 10:48, 30 March 2022

OCA at 12:20, 29 December 2021

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

OCA: New page: '''Unreleased structure''' The entry 7vfb is ON HOLD Authors: Geng, Y., Sun, Z.C., Wang, L. Description: the complex of SARS-CoV2 3cl and NB2B4 Category: Unreleased Structures [[Ca...