5n5o - Revision history

OCA at 18:03, 8 November 2023

OCA — Wed, 08 Nov 2023 18:03:28 GMT

←Older revision		Revision as of 18:03, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='5n5o' size='340' side='right'caption='[[5n5o]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5n5o' size='340' side='right'caption='[[5n5o]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n5o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5O OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5N5O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n5o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N5O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8O5:(2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide'>8O5</scene></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'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5o OCA], [~~http~~://pdbe.org/5n5o PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5n5o RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5n5o PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5o ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8O5:(2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide'>8O5</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=5n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5o OCA], [https://pdbe.org/5n5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n5o RCSB], [https://www.ebi.ac.uk/pdbsum/5n5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5o ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~R1AB_CVHSA R1AB_CVHSA~~]~~] 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 (~~By ~~similarity~~).<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~The papain-like proteinase (PL-PRO) is responsible~~ for the cleavages located at the N-terminus of 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host ~~IRF~~-3.<ref>PMID:~~17024178~~</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> ~~The main proteinase 3CL~~-~~PRO is responsible~~ for ~~the majority of cleavages as it cleaves~~ the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]~~. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity)~~. Also ~~contains~~ an ADP-ribose-1''-phosphate (ADRP)~~-binding function~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~The helicase which contains~~ a ~~zinc finger structure displays RNA and DNA duplex-unwinding activities~~ with ~~5' to 3' polarity. Its ATPase activity is strongly stimulated by poly~~(U)~~, poly(dT), poly(C), poly(dA), but not~~ by ~~poly(G)~~. ~~Activity of helicase is dependent on magnesium~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~The exoribonuclease acts on both ssRNA and dsRNA in~~ a 3' to 5' ~~direction~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~Nsp7-nsp8 hexadecamer may possibly confer processivity~~ to ~~the polymerase~~, ~~maybe by binding to dsRNA or by producing primers utilized by~~ the ~~latter~~.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~Nsp9 is a ssRNA-binding protein.~~<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> <ref>PMID:~~19369340~~</ref> ~~NendoU is a~~ Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:~~17024178~~</ref> <ref>PMID:~~17692280~~</ref> ~~<ref>PMID:19369340</ref>~~	+	[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>
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hilgenfeld, R]]~~	+	[[Category: Severe acute respiratory syndrome-related coronavirus]]
-	~~[[Category: Zhang, L]]~~	+	[[Category: Hilgenfeld R]]
-	~~[[Category: Alpha~~-~~ketoamide~~]]	+	[[Category: Zhang L]]
-	[[Category: ~~Coronavirus~~]]	+
-	[[Category: ~~Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Viral protease~~]]	+

OCA at 11:57, 26 August 2020

OCA — Wed, 26 Aug 2020 11:57:32 GMT

←Older revision		Revision as of 11:57, 26 August 2020
Line 1:		Line 1:

	==Structure of SARS coronavirus main protease in complex with the alpha-ketoamide (S)-N-benzyl-3-((S)-2-cinnamamido-3-cyclopropylpropanamido)-2-oxo-4-((S)-2-oxopyrrolidin-3-yl)butanamide (Cinnamoyl-cyclopropylalanine-GlnLactam-CO-CO-NH-benzyl)==		==Structure of SARS coronavirus main protease in complex with the alpha-ketoamide (S)-N-benzyl-3-((S)-2-cinnamamido-3-cyclopropylpropanamido)-2-oxo-4-((S)-2-oxopyrrolidin-3-yl)butanamide (Cinnamoyl-cyclopropylalanine-GlnLactam-CO-CO-NH-benzyl)==
-	<StructureSection load='5n5o' size='340' side='right' caption='[[5n5o]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5n5o' size='340' side='right'caption='[[5n5o]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n5o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5O OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5N5O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n5o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N5O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8O5:(2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide'>8O5</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8O5:(2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide'>8O5</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5o OCA], [http://pdbe.org/5n5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5o RCSB], [http://www.ebi.ac.uk/pdbsum/5n5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5o ProSAT]</span></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=5n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5o OCA], [http://pdbe.org/5n5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5o RCSB], [http://www.ebi.ac.uk/pdbsum/5n5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5o ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 13:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Hilgenfeld, R]]		[[Category: Hilgenfeld, R]]
	[[Category: Zhang, L]]		[[Category: Zhang, L]]

OCA at 04:58, 8 March 2018

OCA — Thu, 08 Mar 2018 04:58:20 GMT

←Older revision		Revision as of 04:58, 8 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5n5o is ~~ON HOLD~~	+	==Structure of SARS coronavirus main protease in complex with the alpha-ketoamide (S)-N-benzyl-3-((S)-2-cinnamamido-3-cyclopropylpropanamido)-2-oxo-4-((S)-2-oxopyrrolidin-3-yl)butanamide (Cinnamoyl-cyclopropylalanine-GlnLactam-CO-CO-NH-benzyl)==
-		+	<StructureSection load='5n5o' size='340' side='right' caption='[[5n5o]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5n5o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N5O FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8O5:(2~{R},3~{S})-3-[[(2~{S})-3-cyclopropyl-2-[[(~{E})-3-phenylprop-2-enoyl]amino]propanoyl]amino]-2-oxidanyl-4-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]-~{N}-(phenylmethyl)butanamide'>8O5</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5o OCA], [http://pdbe.org/5n5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5o RCSB], [http://www.ebi.ac.uk/pdbsum/5n5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5o ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] 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 (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hilgenfeld, R]]
		+	[[Category: Zhang, L]]
		+	[[Category: Alpha-ketoamide]]
		+	[[Category: Coronavirus]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Viral protease]]

OCA: Protected "5n5o" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 12:05:40 GMT

Protected "5n5o" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:05, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5n5o is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 09 Mar 2017 12:05:39 GMT

New page: '''Unreleased structure''' The entry 5n5o is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5n5o is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]