5hn0 - Revision history

OCA at 10:47, 16 August 2023

OCA — Wed, 16 Aug 2023 10:47:34 GMT

←Older revision		Revision as of 10:47, 16 August 2023
Line 3:		Line 3:
	<StructureSection load='5hn0' size='340' side='right'caption='[[5hn0]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='5hn0' size='340' side='right'caption='[[5hn0]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hn0]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5HN0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hn0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HN0 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=LNN:(6~~-~~HYDROXYBIPHENYL-3-YL)ACETIC+ACID'>LNN</scene>~~, ~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.05Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5hmw\|5hmw]], [[5hmx\|5hmx]], [[5hmy\|5hmy]], [[5hmz\|5hmz]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LNN:(6-HYDROXYBIPHENYL-3-YL)ACETIC+ACID'>LNN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr~~ id~~='activity'><td class~~="~~sblockLbl~~"><~~b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48]~~ </~~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=5hn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn0 OCA], [https://pdbe.org/5hn0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hn0 RCSB], [https://www.ebi.ac.uk/pdbsum/5hn0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn0 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=5hn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn0 OCA], [~~http~~://pdbe.org/5hn0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5hn0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5hn0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~Q6DLV0_9FLAV Q6DLV0_9FLAV~~]~~] Envelope~~ protein E binding to ~~host~~ cell surface ~~receptor is followed~~ by ~~virus internalization~~ through ~~clathrin~~-~~mediated endocytosis~~. ~~Envelope~~ protein E is ~~subsequently involved~~ in ~~membrane~~ fusion ~~between~~ virion and ~~host late endosomes~~. ~~Synthesized as a homodimer with~~ prM ~~which acts as~~ a ~~chaperone for~~ envelope protein E. ~~After cleavage~~ of prM, envelope protein E ~~dissociate~~ from ~~small envelope~~ protein M and ~~homodimerizes~~ (By similarity).[~~SAAS~~:~~SAAS000336_004_099774~~]	+	[https://www.uniprot.org/uniprot/POLG_DEN3S POLG_DEN3S] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions. Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.[UniProtKB:P17763] Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 1: Disrupts the host endothelial glycocalyx layer of host pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. NS1 induces expression of sialidases, heparanase, and activates cathepsin L, which activates heparanase via enzymatic cleavage. These effects are probably linked to the endothelial hyperpermeability observed in severe dengue disease.[UniProtKB:P17763] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.[UniProtKB:P17763] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).[UniProtKB:P17763][PROSITE-ProRule:PRU00859] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction.[PROSITE-ProRule:PRU00860] Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. Plays a role in the inhibition of the host innate immune response. Interacts with host MAVS and thereby prevents the interaction between DDX58 and MAVS. In turn, IFN-beta production is impaired.[UniProtKB:P17763][UniProtKB:Q9Q6P4] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[UniProtKB:P17763] Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.[UniProtKB:Q9Q6P4] RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:P17763]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	[[Category: Dengue virus 3]]		[[Category: Dengue virus 3]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed RNA polymerase]]~~	+	[[Category: Noble CG]]
-	[[Category: Noble~~, C G]]~~	+
-	~~[[Category: Inhibitor complex polymerase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:24, 27 May 2020

OCA — Wed, 27 May 2020 08:24:35 GMT

←Older revision		Revision as of 08:24, 27 May 2020
Line 1:		Line 1:

	==Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4==		==Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4==
-	<StructureSection load='5hn0' size='340' side='right' caption='[[5hn0]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='5hn0' size='340' side='right'caption='[[5hn0]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hn0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5HN0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hn0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HN0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LNN:(6-HYDROXYBIPHENYL-3-YL)ACETIC+ACID'>LNN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LNN:(6-HYDROXYBIPHENYL-3-YL)ACETIC+ACID'>LNN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5hmw\|5hmw]], [[5hmx\|5hmx]], [[5hmy\|5hmy]], [[5hmz\|5hmz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5hmw\|5hmw]], [[5hmx\|5hmx]], [[5hmy\|5hmy]], [[5hmz\|5hmz]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5hn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn0 OCA], [http://pdbe.org/5hn0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hn0 RCSB], [http://www.ebi.ac.uk/pdbsum/5hn0 PDBsum]</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=5hn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn0 OCA], [http://pdbe.org/5hn0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hn0 RCSB], [http://www.ebi.ac.uk/pdbsum/5hn0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5hn0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5hn0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Dengue virus 3]]
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Noble, C G]]		[[Category: Noble, C G]]
	[[Category: Inhibitor complex polymerase]]		[[Category: Inhibitor complex polymerase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 20:36, 11 May 2016

OCA — Wed, 11 May 2016 20:36:32 GMT

←Older revision		Revision as of 20:36, 11 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5hn0 is ~~ON HOLD until Paper~~ Publication	+	==Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4==
		+	<StructureSection load='5hn0' size='340' side='right' caption='[[5hn0]], [[Resolution\|resolution]] 2.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5hn0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HN0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LNN:(6-HYDROXYBIPHENYL-3-YL)ACETIC+ACID'>LNN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5hmw\|5hmw]], [[5hmx\|5hmx]], [[5hmy\|5hmy]], [[5hmz\|5hmz]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn0 OCA], [http://pdbe.org/5hn0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hn0 RCSB], [http://www.ebi.ac.uk/pdbsum/5hn0 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q6DLV0_9FLAV Q6DLV0_9FLAV]] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS000336_004_099774]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery and optimization of non-nucleoside dengue viral RNA-dependent-RNA polymerase (RdRp) inhibitors are described. An X-ray-based fragment screen of Novartis' fragment collection resulted in the identification of a biphenyl acetic acid fragment 3, which bound in the palm subdomain of RdRp. Subsequent optimization of the fragment hit 3, relying on structure-based design, resulted in a >1000-fold improvement in potency in vitro and acquired antidengue activity against all four serotypes with low micromolar EC50 in cell-based assays. The lead candidate 27 interacts with a novel binding pocket in the palm subdomain of the RdRp and exerts a promising activity against all clinically relevant dengue serotypes.

-	~~Authors:~~ Noble, C.G.	+	Discovery of Potent Non-Nucleoside Inhibitors of Dengue Viral RNA-Dependent RNA Polymerase from a Fragment Hit Using Structure-Based Drug Design.,Yokokawa F, Nilar S, Noble CG, Lim SP, Rao R, Tania S, Wang G, Lee G, Hunziker J, Karuna R, Manjunatha U, Shi PY, Smith PW J Med Chem. 2016 Apr 28;59(8):3935-52. doi: 10.1021/acs.jmedchem.6b00143. Epub, 2016 Apr 8. PMID:26984786<ref>PMID:26984786</ref>

-	~~Description: Dengue serotype 3 RNA~~-~~dependent RNA polymerase bound to compound 4~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Noble, C.G]]	+	<div class="pdbe-citations 5hn0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: RNA-directed RNA polymerase]]
		+	[[Category: Noble, C G]]
		+	[[Category: Inhibitor complex polymerase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "5hn0" [edit=sysop:move=sysop]

OCA — Thu, 28 Jan 2016 00:54:29 GMT

Protected "5hn0" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:54, 28 January 2016

OCA: New page: '''Unreleased structure''' The entry 5hn0 is ON HOLD until Paper Publication Authors: Noble, C.G. Description: Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4 [[Cate...

OCA — Thu, 28 Jan 2016 00:54:28 GMT

New page: '''Unreleased structure''' The entry 5hn0 is ON HOLD until Paper Publication Authors: Noble, C.G. Description: Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4 [[Cate...

New page

'''Unreleased structure'''

The entry 5hn0 is ON HOLD until Paper Publication

Authors: Noble, C.G.

Description: Dengue serotype 3 RNA-dependent RNA polymerase bound to compound 4
[[Category: Unreleased Structures]]
[[Category: Noble, C.G]]