5f41 - Revision history

OCA at 08:45, 12 July 2023

2023-07-12T08:45:18Z

←Older revision		Revision as of 08:45, 12 July 2023
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	<StructureSection load='5f41' size='340' side='right'caption='[[5f41]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5f41' size='340' side='right'caption='[[5f41]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5f41]] 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=5F41 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5F41 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5f41]] 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=5F41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F41 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5V6:2-(4-METHOXY-3-THIOPHEN-3-YL-PHENYL)ETHANOIC+ACID'>5V6</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]] 2Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f3z\|5f3z]], [[5fst\|5fst]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5V6:2-(4-METHOXY-3-THIOPHEN-3-YL-PHENYL)ETHANOIC+ACID'>5V6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f41 OCA], [~~http~~://pdbe.org/5f41 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5f41 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5f41 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5f41 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=5f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f41 OCA], [https://pdbe.org/5f41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f41 RCSB], [https://www.ebi.ac.uk/pdbsum/5f41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f41 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: Noble~~, C G]]~~	+	[[Category: Noble CG]]
-	~~[[Category: Dengue virus]]~~	+
-	~~[[Category: Inhibitor rdrp]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:58, 29 April 2020

2020-04-29T07:58:51Z

←Older revision		Revision as of 07:58, 29 April 2020
Line 1:		Line 1:

	==DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26==		==DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26==
-	<StructureSection load='5f41' size='340' side='right' caption='[[5f41]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5f41' size='340' side='right'caption='[[5f41]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5f41]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F41 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5F41 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5f41]] 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=5F41 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F41 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5V6:2-(4-METHOXY-3-THIOPHEN-3-YL-PHENYL)ETHANOIC+ACID'>5V6</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=5V6:2-(4-METHOXY-3-THIOPHEN-3-YL-PHENYL)ETHANOIC+ACID'>5V6</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">[[5f3z\|5f3z]], [[5fst\|5fst]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f3z\|5f3z]], [[5fst\|5fst]]</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=5f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f41 OCA], [http://pdbe.org/5f41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f41 RCSB], [http://www.ebi.ac.uk/pdbsum/5f41 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=5f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f41 OCA], [http://pdbe.org/5f41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f41 RCSB], [http://www.ebi.ac.uk/pdbsum/5f41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f41 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Dengue virus 3]]
		+	[[Category: Large Structures]]
	[[Category: Noble, C G]]		[[Category: Noble, C G]]
	[[Category: Dengue virus]]		[[Category: Dengue virus]]
	[[Category: Inhibitor rdrp]]		[[Category: Inhibitor rdrp]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 08:03, 20 June 2016

2016-06-20T08:03:07Z

←Older revision		Revision as of 08:03, 20 June 2016
Line 10:		Line 10:
	== 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]		[[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 ==
		+	We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using X-ray crystallography. A screen of 1,400 fragments in pools of 8 identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm sub-domain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface-plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene, show higher-affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design.
		+
		+	A Conserved Pocket in the Dengue Virus Polymerase Identified Through Fragment-Based Screening.,Noble CG, Lim SP, Arora R, Yokokawa F, Nilar S, Seh CC, Wright SK, Benson TE, Smith PW, Shi PY J Biol Chem. 2016 Feb 12. pii: jbc.M115.710731. PMID:26872970<ref>PMID:26872970</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5f41" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 18:21, 26 February 2016

2016-02-26T18:21:02Z

←Older revision		Revision as of 18:21, 26 February 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5f41 is ~~ON HOLD until Paper Publication~~	+	==DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26==
-		+	<StructureSection load='5f41' size='340' side='right' caption='[[5f41]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Noble~~, C.G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5f41]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F41 FirstGlance]. <br>
-	~~Description:~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5V6:2-(4-METHOXY-3-THIOPHEN-3-YL-PHENYL)ETHANOIC+ACID'>5V6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f3z\|5f3z]], [[5fst\|5fst]]</td></tr>
-	[[Category: Noble, C.G]]	+	<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=5f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f41 OCA], [http://pdbe.org/5f41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f41 RCSB], [http://www.ebi.ac.uk/pdbsum/5f41 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]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Noble, C G]]
		+	[[Category: Dengue virus]]
		+	[[Category: Inhibitor rdrp]]
		+	[[Category: Transferase]]

OCA at 12:31, 16 December 2015

2015-12-16T12:31:39Z

←Older revision		Revision as of 12:31, 16 December 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5f41 is ON HOLD	+	The entry 5f41 is ON HOLD until Paper Publication

	Authors: Noble, C.G.		Authors: Noble, C.G.

OCA: Protected "5f41" [edit=sysop:move=sysop]

2015-12-09T12:35:36Z

Protected "5f41" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:35, 9 December 2015

OCA: New page: '''Unreleased structure''' The entry 5f41 is ON HOLD Authors: Noble, C.G. Description: Category: Unreleased Structures Category: Noble, C.G

2015-12-09T12:35:35Z

New page: '''Unreleased structure''' The entry 5f41 is ON HOLD Authors: Noble, C.G. Description: Category: Unreleased Structures Category: Noble, C.G

New page

'''Unreleased structure'''

The entry 5f41 is ON HOLD

Authors: Noble, C.G.

Description:
[[Category: Unreleased Structures]]
[[Category: Noble, C.G]]