OCA at 14:21, 18 October 2023

OCA — Wed, 18 Oct 2023 14:21:53 GMT

←Older revision		Revision as of 14:21, 18 October 2023
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	==Structure of SARS main protease bound to inhibitor X47==		==Structure of SARS main protease bound to inhibitor X47==
-	<StructureSection load='6wco' size='340' side='right'caption='[[6wco]]' scene=''>	+	<StructureSection load='6wco' size='340' side='right'caption='[[6wco]], [[Resolution\|resolution]] 1.48Å' 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=6WCO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6WCO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6wco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/SARS_coronavirus_Urbani SARS coronavirus Urbani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WCO FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6wco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wco OCA], [~~http~~://pdbe.org/6wco PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6wco RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6wco PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6wco 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]] 1.48Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=X47:N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclopentylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide'>X47</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=6wco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wco OCA], [https://pdbe.org/6wco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wco RCSB], [https://www.ebi.ac.uk/pdbsum/6wco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wco ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/R1AB_SARS R1AB_SARS] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. 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 (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).<ref>PMID:23035226</ref> <ref>PMID:30943371</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.<ref>PMID:19640993</ref> 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 (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.<ref>PMID:16271890</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> <ref>PMID:24622840</ref> <ref>PMID:24410069</ref> Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.<ref>PMID:23943763</ref> <ref>PMID:24410069</ref> 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). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.[PROSITE-ProRule:PRU00772]<ref>PMID:16226257</ref> Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). 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 (PubMed:24991833).<ref>PMID:24991833</ref> <ref>PMID:24410069</ref> 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.<ref>PMID:22039154</ref> 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.<ref>PMID:22039154</ref> May participate in viral replication by acting as a ssRNA-binding protein.<ref>PMID:19153232</ref> 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.<ref>PMID:22635272</ref> Responsible for replication and transcription of the viral RNA genome.<ref>PMID:22791111</ref> 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.<ref>PMID:12917423</ref> <ref>PMID:22615777</ref> 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 (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585).<ref>PMID:16549795</ref> <ref>PMID:20421945</ref> <ref>PMID:21593585</ref> <ref>PMID:22635272</ref> <ref>PMID:23966862</ref> <ref>PMID:29511076</ref> Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. 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.<ref>PMID:18417574</ref> <ref>PMID:20421945</ref>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: SARS coronavirus Urbani]]
	[[Category: Mesecar AD]]		[[Category: Mesecar AD]]

OCA at 05:34, 5 August 2020

OCA — Wed, 05 Aug 2020 05:34:57 GMT

←Older revision		Revision as of 05:34, 5 August 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6wco is ON HOLD~~	+	==Structure of SARS main protease bound to inhibitor X47==
-		+	<StructureSection load='6wco' size='340' side='right'caption='[[6wco]]' scene=''>
-	~~Authors: Mesecar, A.D., Center for Structural Genomics of Infectious Diseases (CSGID)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WCO FirstGlance]. <br>
-	~~Description:~~ Structure of SARS main protease bound to inhibitor X47	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wco OCA], [http://pdbe.org/6wco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wco RCSB], [http://www.ebi.ac.uk/pdbsum/6wco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wco ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Mesecar~~, A.D]]	+	__TOC__
-	[[Category: ~~Center For Structural Genomics Of Infectious Diseases (Csgid)~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mesecar AD]]

OCA: Protected "6wco" [edit=sysop:move=sysop]

OCA — Wed, 08 Apr 2020 05:36:56 GMT

Protected "6wco" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:36, 8 April 2020

OCA: New page: '''Unreleased structure''' The entry 6wco is ON HOLD Authors: Mesecar, A.D., Center for Structural Genomics of Infectious Diseases (CSGID) Description: Structure of SARS main protease ...

OCA — Wed, 08 Apr 2020 05:36:55 GMT

New page: '''Unreleased structure''' The entry 6wco is ON HOLD Authors: Mesecar, A.D., Center for Structural Genomics of Infectious Diseases (CSGID) Description: Structure of SARS main protease ...

New page

'''Unreleased structure'''

The entry 6wco is ON HOLD

Authors: Mesecar, A.D., Center for Structural Genomics of Infectious Diseases (CSGID)

Description: Structure of SARS main protease bound to inhibitor X47
[[Category: Unreleased Structures]]
[[Category: Mesecar, A.D]]
[[Category: Center For Structural Genomics Of Infectious Diseases (Csgid)]]

6wco - Revision history

OCA at 14:21, 18 October 2023

OCA at 05:34, 5 August 2020

OCA: Protected "6wco" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6wco is ON HOLD Authors: Mesecar, A.D., Center for Structural Genomics of Infectious Diseases (CSGID) Description: Structure of SARS main protease ...