4yoj - Revision history

OCA at 13:04, 1 March 2024

2024-03-01T13:04:17Z

←Older revision		Revision as of 13:04, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tylonycteris_bat_coronavirus_HKU4 Tylonycteris bat coronavirus HKU4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tylonycteris_bat_coronavirus_HKU4 Tylonycteris bat coronavirus HKU4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</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]] 1.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [https://pdbe.org/4yoj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [https://www.ebi.ac.uk/pdbsum/4yoj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoj 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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [https://pdbe.org/4yoj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [https://www.ebi.ac.uk/pdbsum/4yoj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/R1AB_BCHK4 R1AB_BCHK4] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Host translation inhibitor nsp1: 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] Non-structural protein 2: 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] Papain-like proteinase: 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] Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7][PROSITE-ProRule:PRU00772] Non-structural protein 6: 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] Non-structural protein 7: Forms an 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] Non-structural protein 8: Forms an 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] Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Non-structural protein 10: 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] RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Helicase: 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] Guanine-N7 methyltransferase: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity.[UniProtKB:P0C6X7] Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 2'-O-methyltransferase: 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]		[https://www.uniprot.org/uniprot/R1AB_BCHK4 R1AB_BCHK4] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Host translation inhibitor nsp1: 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] Non-structural protein 2: 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] Papain-like proteinase: 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] Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7][PROSITE-ProRule:PRU00772] Non-structural protein 6: 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] Non-structural protein 7: Forms an 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] Non-structural protein 8: Forms an 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] Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Non-structural protein 10: 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] RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Helicase: 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] Guanine-N7 methyltransferase: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity.[UniProtKB:P0C6X7] Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 2'-O-methyltransferase: 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 ==
-	The bat coronavirus HKU4 belongs to the same 2c lineage as that of the deadly Middle East Respiratory Syndrome coronavirus (MERS-CoV) and shows high sequence similarity, therefore potentiating a threat to the human population through a zoonotic shift or 'spill over' event. To date, there are no effective vaccines or antiviral treatments available that are capable of limiting the pathogenesis of any human coronaviral infection. An attractive target for the development of anti-coronaviral therapeutics is the 3C-like protease (3CLpro), which is essential for the progression of the coronaviral life cycle. Herein, we report the screening results of a small, 230-member peptidomimetic library against HKU4-CoV 3CLpro and the identification of 43 peptidomimetic compounds showing good to excellent inhibitory potency of HKU4-CoV 3CLpro with IC50 values ranging from low micromolar to sub-micromolar. We established structure-activity relationships (SARs) describing the important ligand-based features required for potent HKU4-CoV 3CLpro inhibition and identified a seemingly favored peptidic backbone for HKU4-CoV 3CLpro inhibition. To investigate this, a molecular sub-structural analysis of the most potent HKU4-CoV 3CLpro inhibitor was accomplished by the synthesis and testing of the lead peptidomimetic inhibitor's sub-structural components, confirming the activity of the favored backbone (22A) identified via SAR analysis. In order to elucidate the structural reasons for such potent HKU4-CoV 3CLpro inhibition by the peptidomimetics having the 22A backbone, we determined the X-ray structures of HKU4-CoV 3CLpro in complex with three peptidomimetic inhibitors. Sequence alignment of HKU4-CoV 3CLpro, and two other lineage C Betacoronaviruses 3CLpro's, HKU5-CoV and MERS-CoV 3CLpro, show that the active site residues of HKU4-CoV 3CLpro that participate in inhibitor binding are conserved in HKU5-CoV and MERS-CoV 3CLpro. Furthermore, we assayed our most potent HKU4-CoV 3CLpro inhibitor for inhibition of HKU5-CoV 3CLpro and found it to have sub-micromolar inhibitory activity (IC50=0.54+/-0.03muM). The X-ray structures and SAR analysis reveal critical insights into the structure and inhibition of HKU4-CoV 3CLpro, providing fundamental knowledge that may be exploited in the development of anti-coronaviral therapeutics for coronaviruses emerging from zoonotic reservoirs.
-
-	Targeting zoonotic viruses: Structure-based inhibition of the 3C-like protease from bat coronavirus HKU4-The likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS).,St John SE, Tomar S, Stauffer SR, Mesecar AD Bioorg Med Chem. 2015 Jun 19. pii: S0968-0896(15)00533-7. doi:, 10.1016/j.bmc.2015.06.039. PMID:26190463<ref>PMID:26190463</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4yoj" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:22, 3 May 2023

2023-05-03T08:22:49Z

←Older revision		Revision as of 08:22, 3 May 2023
Line 3:		Line 3:
	<StructureSection load='4yoj' size='340' side='right'caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4yoj' size='340' side='right'caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Bchk4 Bchk4~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tylonycteris_bat_coronavirus_HKU4 Tylonycteris bat coronavirus HKU4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yoi\|4yoi]], [[4yo9\|4yo9]], [[4yog\|4yog]]</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [https://pdbe.org/4yoj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [https://www.ebi.ac.uk/pdbsum/4yoj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoj ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=694007 BCHK4])~~</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [~~http~~://pdbe.org/4yoj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4yoj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/R1AB_BCHK4 R1AB_BCHK4]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Host translation inhibitor nsp1: 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] Non-structural protein 2: 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] Papain-like proteinase: 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] Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7][PROSITE-ProRule:PRU00772] Non-structural protein 6: 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] Non-structural protein 7: Forms an 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] Non-structural protein 8: Forms an 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] Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Non-structural protein 10: 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] RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Helicase: 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] Guanine-N7 methyltransferase: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity.[UniProtKB:P0C6X7] Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 2'-O-methyltransferase: 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]	+	[https://www.uniprot.org/uniprot/R1AB_BCHK4 R1AB_BCHK4] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Host translation inhibitor nsp1: 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] Non-structural protein 2: 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] Papain-like proteinase: 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] Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7][PROSITE-ProRule:PRU00772] Non-structural protein 6: 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] Non-structural protein 7: Forms an 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] Non-structural protein 8: Forms an 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] Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Non-structural protein 10: 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] RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Helicase: 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] Guanine-N7 methyltransferase: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity.[UniProtKB:P0C6X7] Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 2'-O-methyltransferase: 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Bchk4]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~John, S E.St~~]]	+	[[Category: Tylonycteris bat coronavirus HKU4]]
-	[[Category: Mesecar, A]]	+	[[Category: Mesecar A]]
-	[[Category: ~~Hku4 3clpro mpro nsp5]]~~	+	[[Category: St John SE]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 15:53, 11 December 2019

2019-12-11T15:53:16Z

←Older revision		Revision as of 15:53, 11 December 2019
Line 1:		Line 1:

	==HKU4 3CLpro bound to non-covalent inhibitor 2A==		==HKU4 3CLpro bound to non-covalent inhibitor 2A==
-	<StructureSection load='4yoj' size='340' side='right' caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4yoj' size='340' side='right'caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bchk4 Bchk4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bchk4 Bchk4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Bchk4]]		[[Category: Bchk4]]
		+	[[Category: Large Structures]]
	[[Category: John, S E.St]]		[[Category: John, S E.St]]
	[[Category: Mesecar, A]]		[[Category: Mesecar, A]]
	[[Category: Hku4 3clpro mpro nsp5]]		[[Category: Hku4 3clpro mpro nsp5]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 15:53, 15 November 2017

2017-11-15T15:53:21Z

←Older revision		Revision as of 15:53, 15 November 2017
Line 1:		Line 1:
		+
	==HKU4 3CLpro bound to non-covalent inhibitor 2A==		==HKU4 3CLpro bound to non-covalent inhibitor 2A==
	<StructureSection load='4yoj' size='340' side='right' caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4yoj' size='340' side='right' caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bchk4 Bchk4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yoi\|4yoi]], [[4yo9\|4yo9]], [[4yog\|4yog]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yoi\|4yoi]], [[4yo9\|4yo9]], [[4yog\|4yog]]</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [http://www.ebi.ac.uk/pdbsum/4yoj PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=694007 BCHK4])</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [http://pdbe.org/4yoj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [http://www.ebi.ac.uk/pdbsum/4yoj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 19:
	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 4yoj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bchk4]]
	[[Category: John, S E.St]]		[[Category: John, S E.St]]
	[[Category: Mesecar, A]]		[[Category: Mesecar, A]]
	[[Category: Hku4 3clpro mpro nsp5]]		[[Category: Hku4 3clpro mpro nsp5]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 19:59, 5 August 2015

2015-08-05T19:59:35Z

←Older revision		Revision as of 19:59, 5 August 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==HKU4 3CLpro bound to non-covalent inhibitor 2A==
		+	<StructureSection load='4yoj' size='340' side='right' caption='[[4yoj]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4yoj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=RFM:N-{4-[(1H-BENZOTRIAZOL-1-YLACETYL)(THIOPHEN-3-YLMETHYL)AMINO]PHENYL}BENZAMIDE'>RFM</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yoi\|4yoi]], [[4yo9\|4yo9]], [[4yog\|4yog]]</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=4yoj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yoj RCSB], [http://www.ebi.ac.uk/pdbsum/4yoj PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/R1AB_BCHK4 R1AB_BCHK4]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.[UniProtKB:P0C6X7] Host translation inhibitor nsp1: 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] Non-structural protein 2: 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] Papain-like proteinase: 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] Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7][PROSITE-ProRule:PRU00772] Non-structural protein 6: 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] Non-structural protein 7: Forms an 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] Non-structural protein 8: Forms an 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] Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Non-structural protein 10: 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] RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Helicase: 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] Guanine-N7 methyltransferase: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity.[UniProtKB:P0C6X7] Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] 2'-O-methyltransferase: 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 ==
		+	The bat coronavirus HKU4 belongs to the same 2c lineage as that of the deadly Middle East Respiratory Syndrome coronavirus (MERS-CoV) and shows high sequence similarity, therefore potentiating a threat to the human population through a zoonotic shift or 'spill over' event. To date, there are no effective vaccines or antiviral treatments available that are capable of limiting the pathogenesis of any human coronaviral infection. An attractive target for the development of anti-coronaviral therapeutics is the 3C-like protease (3CLpro), which is essential for the progression of the coronaviral life cycle. Herein, we report the screening results of a small, 230-member peptidomimetic library against HKU4-CoV 3CLpro and the identification of 43 peptidomimetic compounds showing good to excellent inhibitory potency of HKU4-CoV 3CLpro with IC50 values ranging from low micromolar to sub-micromolar. We established structure-activity relationships (SARs) describing the important ligand-based features required for potent HKU4-CoV 3CLpro inhibition and identified a seemingly favored peptidic backbone for HKU4-CoV 3CLpro inhibition. To investigate this, a molecular sub-structural analysis of the most potent HKU4-CoV 3CLpro inhibitor was accomplished by the synthesis and testing of the lead peptidomimetic inhibitor's sub-structural components, confirming the activity of the favored backbone (22A) identified via SAR analysis. In order to elucidate the structural reasons for such potent HKU4-CoV 3CLpro inhibition by the peptidomimetics having the 22A backbone, we determined the X-ray structures of HKU4-CoV 3CLpro in complex with three peptidomimetic inhibitors. Sequence alignment of HKU4-CoV 3CLpro, and two other lineage C Betacoronaviruses 3CLpro's, HKU5-CoV and MERS-CoV 3CLpro, show that the active site residues of HKU4-CoV 3CLpro that participate in inhibitor binding are conserved in HKU5-CoV and MERS-CoV 3CLpro. Furthermore, we assayed our most potent HKU4-CoV 3CLpro inhibitor for inhibition of HKU5-CoV 3CLpro and found it to have sub-micromolar inhibitory activity (IC50=0.54+/-0.03muM). The X-ray structures and SAR analysis reveal critical insights into the structure and inhibition of HKU4-CoV 3CLpro, providing fundamental knowledge that may be exploited in the development of anti-coronaviral therapeutics for coronaviruses emerging from zoonotic reservoirs.

-	The ~~entry 4yoj is ON HOLD until Paper Publication~~	+	Targeting zoonotic viruses: Structure-based inhibition of the 3C-like protease from bat coronavirus HKU4-The likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS).,St John SE, Tomar S, Stauffer SR, Mesecar AD Bioorg Med Chem. 2015 Jun 19. pii: S0968-0896(15)00533-7. doi:, 10.1016/j.bmc.2015.06.039. PMID:26190463<ref>PMID:26190463</ref>

-	~~Authors: St~~. ~~John,~~ S.~~E., Mesecar, A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: HKU4 3CLpro bound to non-covalent inhibitor 2A~~	+	== References ==
-	~~[[Category: Unreleased Structures]]~~	+	<references/>
-	[[Category: ~~St.~~ John, S.E]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: John, S E.St]]
	[[Category: Mesecar, A]]		[[Category: Mesecar, A]]
		+	[[Category: Hku4 3clpro mpro nsp5]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 09:33, 30 April 2015

2015-04-30T09:33:34Z

←Older revision		Revision as of 09:33, 30 April 2015
Line 3:		Line 3:
	The entry 4yoj is ON HOLD until Paper Publication		The entry 4yoj is ON HOLD until Paper Publication

-	Authors: St.John, S.E., Mesecar, A.	+	Authors: St. John, S.E., Mesecar, A.

	Description: HKU4 3CLpro bound to non-covalent inhibitor 2A		Description: HKU4 3CLpro bound to non-covalent inhibitor 2A
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: St.John, S.E]]	+	[[Category: St. John, S.E]]
	[[Category: Mesecar, A]]		[[Category: Mesecar, A]]

OCA at 09:40, 8 April 2015

2015-04-08T09:40:59Z

←Older revision		Revision as of 09:40, 8 April 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4yoj is ON HOLD	+	The entry 4yoj is ON HOLD until Paper Publication

	Authors: St.John, S.E., Mesecar, A.		Authors: St.John, S.E., Mesecar, A.

OCA at 11:44, 1 April 2015

2015-04-01T11:44:08Z

←Older revision		Revision as of 11:44, 1 April 2015
Line 3:		Line 3:
	The entry 4yoj is ON HOLD		The entry 4yoj is ON HOLD

-	Authors: St.John, ~~Sarah~~ E., Mesecar, A.	+	Authors: St.John, S.E., Mesecar, A.

	Description: HKU4 3CLpro bound to non-covalent inhibitor 2A		Description: HKU4 3CLpro bound to non-covalent inhibitor 2A
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: St.John, S.E]]
	[[Category: Mesecar, A]]		[[Category: Mesecar, A]]
-	[[Category: St.John, Sarah E]]

OCA at 12:38, 26 March 2015

2015-03-26T12:38:33Z

←Older revision		Revision as of 12:38, 26 March 2015
Line 3:		Line 3:
	The entry 4yoj is ON HOLD		The entry 4yoj is ON HOLD

-	Authors: St. John, Sarah E.	+	Authors: St.John, Sarah E., Mesecar, A.

	Description: HKU4 3CLpro bound to non-covalent inhibitor 2A		Description: HKU4 3CLpro bound to non-covalent inhibitor 2A
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: St. John, Sarah E]]	+	[[Category: Mesecar, A]]
		+	[[Category: St.John, Sarah E]]

OCA: Protected "4yoj" [edit=sysop:move=sysop]

2015-03-18T10:57:57Z

Protected "4yoj" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:57, 18 March 2015