6w5j - Revision history

OCA at 14:17, 18 October 2023

OCA — Wed, 18 Oct 2023 14:17:22 GMT

←Older revision		Revision as of 14:17, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='6w5j' size='340' side='right'caption='[[6w5j]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='6w5j' size='340' side='right'caption='[[6w5j]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6w5j]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Hu/nv/nv~~/1968/us Hu~~/nv/nv~~/1968/us]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5J OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6W5J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w5j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Norovirus_Hu/1968/US Norovirus Hu/1968/US]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W5J FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TKS:2-(3-chlorophenyl)-2-methylpropyl+[(2S)-3-cyclohexyl-1-({(1R,2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]-1-sulfanylpropan-2-yl}amino)-1-oxopropan-2-yl]carbamate'>TKS</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ORF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=524364 Hu/NV/NV/1968/US])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TKS:2-(3-chlorophenyl)-2-methylpropyl+[(2S)-3-cyclohexyl-1-({(1R,2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]-1-sulfanylpropan-2-yl}amino)-1-oxopropan-2-yl]carbamate'>TKS</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calicivirin Calicivirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.66 3.4.22.66] </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=6w5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5j OCA], [https://pdbe.org/6w5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w5j RCSB], [https://www.ebi.ac.uk/pdbsum/6w5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5j 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=6w5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5j OCA], [~~http~~://pdbe.org/6w5j PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6w5j RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6w5j PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5j ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POLG_NVN68 POLG_NVN68]] Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Protein P22 may play a role in targeting replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref> RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref>	+	[https://www.uniprot.org/uniprot/POLG_NVN68 POLG_NVN68] Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Protein P22 may play a role in targeting replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref> RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6w5j" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6w5j" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Calicivirin]]
-	[[Category: Hu/nv/nv/1968/us]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Battaile~~, K P~~]]	+	[[Category: Norovirus Hu/1968/US]]
-	[[Category: Chang~~, K O~~]]	+	[[Category: Battaile KP]]
-	[[Category: Groutas~~, W C~~]]	+	[[Category: Chang KO]]
-	[[Category: Kashipathy~~, M M~~]]	+	[[Category: Groutas WC]]
-	[[Category: Kim, Y]]	+	[[Category: Kashipathy MM]]
-	[[Category: Lovell, S]]	+	[[Category: Kim Y]]
-	[[Category: Rathnayake~~, A D]]~~	+	[[Category: Lovell S]]
-	~~[[Category: Hydrolase]]~~	+	[[Category: Rathnayake AD]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Norovirus 3cl protease]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 07:36, 4 November 2020

OCA — Wed, 04 Nov 2020 07:36:55 GMT

←Older revision		Revision as of 07:36, 4 November 2020
Line 1:		Line 1:

	==1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d==		==1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d==
-	<StructureSection load='6w5j' size='340' side='right'caption='[[6w5j]]' scene=''>	+	<StructureSection load='6w5j' size='340' side='right'caption='[[6w5j]], [[Resolution\|resolution]] 1.85Å' 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=6W5J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W5J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w5j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hu/nv/nv/1968/us Hu/nv/nv/1968/us]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W5J 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=6w5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5j OCA], [http://pdbe.org/6w5j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w5j RCSB], [http://www.ebi.ac.uk/pdbsum/6w5j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5j 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=TKS:2-(3-chlorophenyl)-2-methylpropyl+[(2S)-3-cyclohexyl-1-({(1R,2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]-1-sulfanylpropan-2-yl}amino)-1-oxopropan-2-yl]carbamate'>TKS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ORF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=524364 Hu/NV/NV/1968/US])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calicivirin Calicivirin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.66 3.4.22.66] </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=6w5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5j OCA], [http://pdbe.org/6w5j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w5j RCSB], [http://www.ebi.ac.uk/pdbsum/6w5j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5j ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_NVN68 POLG_NVN68]] Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Protein P22 may play a role in targeting replication complex to intracellular membranes.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation.<ref>PMID:569187</ref> <ref>PMID:11160659</ref> 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref> RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).<ref>PMID:569187</ref> <ref>PMID:11160659</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Acute gastroenteritis caused by noroviruses has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The disease impacts most severely immunocompromised patients, the elderly, and children. The current lack of approved vaccines and small-molecule therapeutics for the treatment and prophylaxis of norovirus infections underscores the need for the development of norovirus-specific drugs. The studies described herein entail the use of the gem-dimethyl moiety as a means of improving the pharmacological activity and physicochemical properties of a dipeptidyl series of transition state inhibitors of norovirus 3CL protease, an enzyme essential for viral replication. Several compounds were found to be potent inhibitors of the enzyme in biochemical and cell-based assays. The pharmacological activity and cellular permeability of the inhibitors were found to be sensitive to the location of the gem-dimethyl group.
		+
		+	Structure-Guided Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease.,Rathnayake AD, Kim Y, Dampalla CS, Nguyen HN, Jesri AM, Kashipathy MM, Lushington GH, Battaile KP, Lovell S, Chang KO, Groutas WC J Med Chem. 2020 Sep 18. doi: 10.1021/acs.jmedchem.0c01252. PMID:32945669<ref>PMID:32945669</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w5j" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Calicivirin]]
		+	[[Category: Hu/nv/nv/1968/us]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Battaile KP]]	+	[[Category: Battaile, K P]]
-	[[Category: Chang KO]]	+	[[Category: Chang, K O]]
-	[[Category: Groutas WC]]	+	[[Category: Groutas, W C]]
-	[[Category: Kashipathy MM]]	+	[[Category: Kashipathy, M M]]
-	[[Category: Kim Y]]	+	[[Category: Kim, Y]]
-	[[Category: Lovell S]]	+	[[Category: Lovell, S]]
-	[[Category: Rathnayake AD]]	+	[[Category: Rathnayake, A D]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Norovirus 3cl protease]]
		+	[[Category: Protease]]

OCA at 07:09, 30 September 2020

OCA — Wed, 30 Sep 2020 07:09:20 GMT

←Older revision		Revision as of 07:09, 30 September 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6w5j ~~is ON HOLD~~	+	==1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d==
-		+	<StructureSection load='6w5j' size='340' side='right'caption='[[6w5j]]' scene=''>
-	~~Authors~~: ~~Lovell, S~~.~~, Kashipathy, M~~.M.~~, Battaile, K~~.P., ~~Rathnayake, A~~.D., ~~Kim~~, Y., ~~Chang, K~~.O., ~~Groutas, W~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W5J FirstGlance]. <br>
-	~~Description: 1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d~~	+	</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=6w5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5j OCA], [http://pdbe.org/6w5j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w5j RCSB], [http://www.ebi.ac.uk/pdbsum/6w5j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5j ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Battaile~~, K.P~~]]	+	__TOC__
-	[[Category: ~~Lovell, S~~]]	+	</StructureSection>
-	[[Category: Groutas~~, W.C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Chang, K.O~~]]	+	[[Category: Battaile KP]]
-	[[Category: ~~Kashipathy, M.M~~]]	+	[[Category: Chang KO]]
-	[[Category: ~~Kim, Y~~]]	+	[[Category: Groutas WC]]
-	[[Category: Rathnayake~~, A.D~~]]	+	[[Category: Kashipathy MM]]
		+	[[Category: Kim Y]]
		+	[[Category: Lovell S]]
		+	[[Category: Rathnayake AD]]

OCA: Protected "6w5j" [edit=sysop:move=sysop]

OCA — Fri, 27 Mar 2020 08:23:20 GMT

Protected "6w5j" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:23, 27 March 2020

OCA: New page: '''Unreleased structure''' The entry 6w5j is ON HOLD Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Rathnayake, A.D., Kim, Y., Chang, K.O., Groutas, W.C. Description: 1.85 A re...

OCA — Fri, 27 Mar 2020 08:23:19 GMT

New page: '''Unreleased structure''' The entry 6w5j is ON HOLD Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Rathnayake, A.D., Kim, Y., Chang, K.O., Groutas, W.C. Description: 1.85 A re...

New page

'''Unreleased structure'''

The entry 6w5j is ON HOLD

Authors: Lovell, S., Kashipathy, M.M., Battaile, K.P., Rathnayake, A.D., Kim, Y., Chang, K.O., Groutas, W.C.

Description: 1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d
[[Category: Unreleased Structures]]
[[Category: Battaile, K.P]]
[[Category: Lovell, S]]
[[Category: Groutas, W.C]]
[[Category: Chang, K.O]]
[[Category: Kashipathy, M.M]]
[[Category: Kim, Y]]
[[Category: Rathnayake, A.D]]