2amd - Revision history

OCA at 00:46, 21 November 2024

2024-11-21T00:46:59Z

← Older revision		Revision as of 00:46, 21 November 2024
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	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [https://pdbe.org/2amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [https://www.ebi.ac.uk/pdbsum/2amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [https://pdbe.org/2amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [https://www.ebi.ac.uk/pdbsum/2amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2amd_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2amd_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 08:18, 15 May 2024

2024-05-15T08:18:49Z

← Older revision		Revision as of 08:18, 15 May 2024
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	<StructureSection load='2amd' size='340' side='right'caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='2amd' size='340' side='right'caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Cvhsa Cvhsa~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[2amd]] is a 2 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=2AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</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]] 1.85Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</div~~></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [https://pdbe.org/2amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [https://www.ebi.ac.uk/pdbsum/2amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [https://pdbe.org/2amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [https://www.ebi.ac.uk/pdbsum/2amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Cvhsa]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bartlam, M]]		[[Category: Severe acute respiratory syndrome-related coronavirus]]
	[[Category: Rao, Z]]		[[Category: Bartlam M]]
	[[Category: Xue, X]]		[[Category: Rao Z]]
	[[Category: Yang, H]]		[[Category: Xue X]]
	[[Category: Yang, K]]		[[Category: Yang H]]
	[[Category: Zhao, Q]]		[[Category: Yang K]]
	~~[[Category: Anti-parallel a-helice]]~~		[[Category: Zhao Q]]
	~~[[Category: Anti-parallel b-barrel]]~~
	~~[[Category: Hydrolase~~]]

OCA at 12:11, 27 April 2022

2022-04-27T12:11:11Z

← Older revision		Revision as of 12:11, 27 April 2022
Line 3:		Line 3:
	<StructureSection load='2amd' size='340' side='right'caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='2amd' size='340' side='right'caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</div></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [~~http~~://pdbe.org/2amd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2amd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [https://pdbe.org/2amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [https://www.ebi.ac.uk/pdbsum/2amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd 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_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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 31:

	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
	*[[Virus ~~proteases~~ 3D ~~strutures~~\|Virus ~~proteases~~ 3D ~~strutures~~]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:08, 22 July 2020

2020-07-22T12:08:23Z

← Older revision		Revision as of 12:08, 22 July 2020
Line 1:		Line 1:

	==Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9==		==Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9==
	<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='2amd' size='340' side='right'caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://pdbe.org/2amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd 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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://pdbe.org/2amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 32:		Line 32:
	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
	*[[~~3C protease~~\|~~3C protease~~]]		*[[Virus proteases 3D strutures\|Virus proteases 3D strutures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Cvhsa]]		[[Category: Cvhsa]]
			[[Category: Large Structures]]
	[[Category: Bartlam, M]]		[[Category: Bartlam, M]]
	[[Category: Rao, Z]]		[[Category: Rao, Z]]

OCA at 07:11, 9 May 2018

2018-05-09T07:11:45Z

← Older revision		Revision as of 07:11, 9 May 2018
Line 1:		Line 1:

	==Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9==		==Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9==
	<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://pdbe.org/2amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://pdbe.org/2amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2amd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2amd_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2amd_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 31:		Line 32:
	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
			*[[3C protease\|3C protease]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:07, 9 February 2016

2016-02-09T19:07:30Z

← Older revision		Revision as of 19:07, 9 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2amd ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:12, 11 September 2015

2015-09-11T01:12:22Z

← Older revision		Revision as of 01:12, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Sars_coronavirus Sars coronavirus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://pdbe.org/2amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 27:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2amd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Sars coronavirus~~]]		[[Category: Cvhsa]]
	[[Category: Bartlam, M]]		[[Category: Bartlam, M]]
	[[Category: Rao, Z]]		[[Category: Rao, Z]]

OCA at 08:54, 25 December 2014

2014-12-25T08:54:47Z

← Older revision		Revision as of 08:54, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></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=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></td></tr>
	<table>		</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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Bartlam, M.]]		[[Category: Bartlam, M]]
	[[Category: Rao, Z.]]		[[Category: Rao, Z]]
	[[Category: Xue, X.]]		[[Category: Xue, X]]
	[[Category: Yang, H.]]		[[Category: Yang, H]]
	[[Category: Yang, K.]]		[[Category: Yang, K]]
	[[Category: Zhao, Q.]]		[[Category: Zhao, Q]]
	[[Category: Anti-parallel a-helice]]		[[Category: Anti-parallel a-helice]]
	[[Category: Anti-parallel b-barrel]]		[[Category: Anti-parallel b-barrel]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 04:08, 29 September 2014

2014-09-29T04:08:29Z

← Older revision		Revision as of 04:08, 29 September 2014
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	[[Image:~~2amd~~.~~png~~\|~~left~~\|~~200px~~]]		==Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9==
			<StructureSection load='2amd' size='340' side='right' caption='[[2amd]], [[Resolution\|resolution]] 1.85Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AMD FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9IN:N-(3-FUROYL)-D-VALYL-L-VALYL-N~1~-((1R,2Z)-4-ETHOXY-4-OXO-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-D-LEUCINAMIDE'>9IN</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1uj1\|1uj1]], [[2amp\|2amp]], [[2amq\|2amq]]</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2amd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2amd RCSB], [http://www.ebi.ac.uk/pdbsum/2amd PDBsum]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2amd_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of Mpro-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.

	~~{{STRUCTURE_2amd\| PDB=2amd \| SCENE= }}~~		Design of wide-spectrum inhibitors targeting coronavirus main proteases.,Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, Zhao Q, Zhou Z, Pei D, Ziebuhr J, Hilgenfeld R, Yuen KY, Wong L, Gao G, Chen S, Chen Z, Ma D, Bartlam M, Rao Z PLoS Biol. 2005 Oct;3(10):e324. Epub 2005 Sep 6. PMID:16128623<ref>PMID:16128623</ref>

	~~===Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N9===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_16128623}}~~

	~~==About this Structure==~~
	~~[[2amd]] is~~ a ~~2 chain structure with sequence from [http://en.wikipedia~~.~~org/wiki/Sars_coronavirus Sars coronavirus]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin~~/~~ocashort?id=2AMD OCA].~~

	==See Also==		==See Also==
	*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]		*[[SARS Coronavirus Main Proteinase\|SARS Coronavirus Main Proteinase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:016128623<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Sars coronavirus]]		[[Category: Sars coronavirus]]
	[[Category: Bartlam, M.]]		[[Category: Bartlam, M.]]

OCA at 14:50, 20 October 2012

2012-10-20T14:50:26Z

← Older revision		Revision as of 14:50, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[2amd]] is a 2 chain structure ~~of [[SARS Coronavirus Main Proteinase]]~~ with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA].		[[2amd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AMD OCA].

	==See Also==		==See Also==