5s4i - Revision history

OCA at 14:13, 6 March 2024

OCA — Wed, 06 Mar 2024 14:13:22 GMT

←Older revision		Revision as of 14:13, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]], [[Resolution\|resolution]] 1.13Å' scene=''>		<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]], [[Resolution\|resolution]] 1.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5s4i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~2019-ncov 2019-ncov~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5s4i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=W3Y:(5S)~~-1~~-(4-chlorophenyl)-5-methylimidazolidine-2,4-dione'>W3Y</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]] 1.131Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~rep, 1a~~-1b (~~[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019~~-~~nCoV]~~)</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W3Y:(5S)-1-(4-chlorophenyl)-5-methylimidazolidine-2,4-dione'>W3Y</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=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [https://pdbe.org/5s4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [https://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i 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=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [https://pdbe.org/5s4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [https://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]	+	[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.	+
-		+
-	Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.,Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Diaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I Sci Adv. 2021 Apr 14;7(16). pii: 7/16/eabf8711. doi: 10.1126/sciadv.abf8711., Print 2021 Apr. PMID:33853786<ref>PMID:33853786</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5s4i" style="background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ahel, I]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: Aimon, A]]	+	[[Category: Ahel I]]
-	[[Category: Brandao-Neto, J]]	+	[[Category: Aimon A]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Brandao-Neto J]]
-	[[Category: Dias, A]]	+	[[Category: Dias A]]
-	[[Category: Douangamath, A]]	+	[[Category: Douangamath A]]
-	[[Category: Dunnet, L]]	+	[[Category: Dunnet L]]
-	[[Category: Fearon, D]]	+	[[Category: Fearon D]]
-	[[Category: Gorrie-Stone~~, T J~~]]	+	[[Category: Gorrie-Stone TJ]]
-	[[Category: Krojer, T]]	+	[[Category: Krojer T]]
-	[[Category: Powell~~, A J~~]]	+	[[Category: Powell AJ]]
-	[[Category: Rack~~, J G.M~~]]	+	[[Category: Rack JGM]]
-	[[Category: Rangel~~, V L~~]]	+	[[Category: Rangel VL]]
-	[[Category: Schuller, M]]	+	[[Category: Schuller M]]
-	[[Category: Skyner, R]]	+	[[Category: Skyner R]]
-	[[Category: Thompson, W]]	+	[[Category: Thompson W]]
-	[[Category: Zhu, K]]	+	[[Category: Zhu K]]
-	[[Category: ~~Pandda]]~~	+	[[Category: Von Delft F]]
-	~~[[Category: Sars-cov-2 nsp3 macrodomain]]~~	+
-	~~[[Category: Sgc - diamond i04-1 fragment screening]]~~	+
-	~~[[Category: Viral protein]]~~	+
-	~~[[Category: Xchemexplorer~~]]	+

OCA at 09:56, 14 July 2021

OCA — Wed, 14 Jul 2021 09:56:32 GMT

←Older revision		Revision as of 09:56, 14 July 2021
Line 1:		Line 1:

	==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with SF051==		==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with SF051==
-	<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]]' scene=''>	+	<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]], [[Resolution\|resolution]] 1.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5s4i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [https://pdbe.org/5s4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [https://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W3Y:(5S)-1-(4-chlorophenyl)-5-methylimidazolidine-2,4-dione'>W3Y</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">rep, 1a-1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [https://pdbe.org/5s4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [https://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2]] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-\|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
		+
		+	Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.,Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Diaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I Sci Adv. 2021 Apr 14;7(16). pii: 7/16/eabf8711. doi: 10.1126/sciadv.abf8711., Print 2021 Apr. PMID:33853786<ref>PMID:33853786</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5s4i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ahel I]]	+	[[Category: Ahel, I]]
-	[[Category: Aimon A]]	+	[[Category: Aimon, A]]
-	[[Category: Brandao-Neto J]]	+	[[Category: Brandao-Neto, J]]
-	[[Category: Dias A]]	+	[[Category: Delft, F von]]
-	[[Category: Douangamath A]]	+	[[Category: Dias, A]]
-	[[Category: Dunnet L]]	+	[[Category: Douangamath, A]]
-	[[Category: Fearon D]]	+	[[Category: Dunnet, L]]
-	[[Category: Gorrie-Stone TJ]]	+	[[Category: Fearon, D]]
-	[[Category: Krojer T]]	+	[[Category: Gorrie-Stone, T J]]
-	[[Category: Powell AJ]]	+	[[Category: Krojer, T]]
-	[[Category: Rack ~~JGM~~]]	+	[[Category: Powell, A J]]
-	[[Category: Rangel VL]]	+	[[Category: Rack, J G.M]]
-	[[Category: Schuller M]]	+	[[Category: Rangel, V L]]
-	[[Category: Skyner R]]	+	[[Category: Schuller, M]]
-	[[Category: Thompson W]]	+	[[Category: Skyner, R]]
-	[[Category: Zhu K]]	+	[[Category: Thompson, W]]
-	[[Category: ~~Von Delft F~~]]	+	[[Category: Zhu, K]]
		+	[[Category: Pandda]]
		+	[[Category: Sars-cov-2 nsp3 macrodomain]]
		+	[[Category: Sgc - diamond i04-1 fragment screening]]
		+	[[Category: Viral protein]]
		+	[[Category: Xchemexplorer]]

OCA at 10:04, 7 July 2021

OCA — Wed, 07 Jul 2021 10:04:28 GMT

←Older revision		Revision as of 10:04, 7 July 2021
Line 3:		Line 3:
	<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]]' scene=''>		<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [~~http~~://pdbe.org/5s4i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>	+	</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=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [https://pdbe.org/5s4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [https://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__

OCA at 05:45, 20 January 2021

OCA — Wed, 20 Jan 2021 05:45:26 GMT

←Older revision		Revision as of 05:45, 20 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5s4i ~~is ON HOLD~~	+	==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with SF051==
-		+	<StructureSection load='5s4i' size='340' side='right'caption='[[5s4i]]' scene=''>
-	~~Authors~~: ~~Fearon, D~~.~~, Schuller, M~~.~~, Rangel, V~~.L.~~, Douangamath, A~~.~~, Rack, J~~.G.M.~~, Zhu, K~~., ~~Aimon, A~~.~~, Brandao-Neto, J~~.~~, Dias, A~~.~~, Dunnet, L., Gorrie~~-~~Stone~~, ~~T.J~~., ~~Powell, A~~.J.~~, Krojer, T~~., ~~Skyner, R~~.~~, Thompson, W~~.~~, Ahel, I~~., ~~von Delft, F~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5S4I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5S4I FirstGlance]. <br>
-	~~Description: PanDDA analysis group deposition --Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with SF051~~	+	</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=5s4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5s4i OCA], [http://pdbe.org/5s4i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5s4i RCSB], [http://www.ebi.ac.uk/pdbsum/5s4i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5s4i ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Aimon, A~~]]	+	__TOC__
-	[[Category: ~~Rangel, V.L~~]]	+	</StructureSection>
-	[[Category: Brandao-Neto, J]]	+	[[Category: Large Structures]]
-	[[Category: ~~Rack, J.G.M~~]]	+	[[Category: Ahel I]]
-	[[Category: ~~Fearon, D~~]]	+	[[Category: Aimon A]]
-	[[Category: ~~Thompson, W~~]]	+	[[Category: Brandao-Neto J]]
-	[[Category: ~~Von Delft, F~~]]	+	[[Category: Dias A]]
-	[[Category: ~~Powell, A.J~~]]	+	[[Category: Douangamath A]]
-	[[Category: ~~Ahel, I~~]]	+	[[Category: Dunnet L]]
-	[[Category: ~~Zhu, K~~]]	+	[[Category: Fearon D]]
-	[[Category: ~~Dunnet, L~~]]	+	[[Category: Gorrie-Stone TJ]]
-	[[Category: ~~Skyner, R~~]]	+	[[Category: Krojer T]]
-	[[Category: ~~Douangamath, A~~]]	+	[[Category: Powell AJ]]
-	[[Category: ~~Krojer, T~~]]	+	[[Category: Rack JGM]]
-	[[Category: ~~Schuller, M~~]]	+	[[Category: Rangel VL]]
-	[[Category: ~~Gorrie-Stone, T.J~~]]	+	[[Category: Schuller M]]
-	[[Category: ~~Dias, A~~]]	+	[[Category: Skyner R]]
		+	[[Category: Thompson W]]
		+	[[Category: Zhu K]]
		+	[[Category: Von Delft F]]

OCA: Protected "5s4i" [edit=sysop:move=sysop]

OCA — Wed, 11 Nov 2020 06:09:12 GMT

Protected "5s4i" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:09, 11 November 2020

OCA: New page: '''Unreleased structure''' The entry 5s4i is ON HOLD Authors: Fearon, D., Schuller, M., Rangel, V.L., Douangamath, A., Rack, J.G.M., Zhu, K., Aimon, A., Brandao-Neto, J., Dias, A., Dunn...

OCA — Wed, 11 Nov 2020 06:09:10 GMT

New page: '''Unreleased structure''' The entry 5s4i is ON HOLD Authors: Fearon, D., Schuller, M., Rangel, V.L., Douangamath, A., Rack, J.G.M., Zhu, K., Aimon, A., Brandao-Neto, J., Dias, A., Dunn...

New page

'''Unreleased structure'''

The entry 5s4i is ON HOLD

Authors: Fearon, D., Schuller, M., Rangel, V.L., Douangamath, A., Rack, J.G.M., Zhu, K., Aimon, A., Brandao-Neto, J., Dias, A., Dunnet, L., Gorrie-Stone, T.J., Powell, A.J., Krojer, T., Skyner, R., Thompson, W., Ahel, I., von Delft, F.

Description: PanDDA analysis group deposition --Crystal Structure of SARS-CoV-2 Nsp3 macrodomain in complex with SF051
[[Category: Unreleased Structures]]
[[Category: Aimon, A]]
[[Category: Rangel, V.L]]
[[Category: Brandao-Neto, J]]
[[Category: Rack, J.G.M]]
[[Category: Fearon, D]]
[[Category: Thompson, W]]
[[Category: Von Delft, F]]
[[Category: Powell, A.J]]
[[Category: Ahel, I]]
[[Category: Zhu, K]]
[[Category: Dunnet, L]]
[[Category: Skyner, R]]
[[Category: Douangamath, A]]
[[Category: Krojer, T]]
[[Category: Schuller, M]]
[[Category: Gorrie-Stone, T.J]]
[[Category: Dias, A]]