3lkw - Revision history

OCA at 08:46, 7 February 2024

OCA — Wed, 07 Feb 2024 08:46:37 GMT

←Older revision		Revision as of 08:46, 7 February 2024
Line 3:		Line 3:
	<StructureSection load='3lkw' size='340' side='right'caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3lkw' size='340' side='right'caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Den1w Den1w~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LKW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_1_Nauru/West_Pac/1974 Dengue virus 1 Nauru/West Pac/1974] and [https://en.wikipedia.org/wiki/Dengue_virus_1_Singapore/S275/1990 Dengue virus 1 Singapore/S275/1990]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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"><div style='overflow: auto; max-height: 3em;'>[[3l6p\|3l6p]]</div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [https://pdbe.org/3lkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [https://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw 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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [https://pdbe.org/3lkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [https://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~POLG_DEN1S POLG_DEN1S~~]~~] Protein~~ C~~: Plays a role~~ in ~~virus budding by binding to 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 in host cytoplasm after hemifusion induced by surface proteins. Can migrate tot cell nucleus where it modulates host functions.[UniProtKB:P17763]~~ 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. Presumably~~ to avoid catastrophic activation of the viral fusion ~~activity in~~ acidic ~~GolGi compartment prior to virion release. prM~~-E cleavage is ~~ineficient,~~ 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 extodomain. 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 particule 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 ineficient,~~ 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~~. ~~May play a role in viral genome replication. Assist~~ membrane ~~bending~~ and ~~envelopment~~ of ~~genomic RNA at the endoplasmic reticulum~~. ~~Excreted as a hexameric lipoparticle that plays a role against host immune responce.[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]~~ Non-structural protein 2B~~: Required~~ cofactor for the serine protease function of NS3 (By similarity). ~~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~~: Induces~~ host endoplasmic regulate the ATPase activity of the NS3 helicase.~~[UniProtKB:P17763]~~ 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~~: 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:P17763]~~ RNA-directed RNA polymerase NS5~~: Replicates~~ the viral (+) and (-) 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 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]~~	+	[https://www.uniprot.org/uniprot/POLG_DEN1W POLG_DEN1W] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). 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). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). 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 (By similarity). Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). Non-structural protein 4B 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 (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) 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 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 (By similarity).
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (~~DEN1 to -4~~). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication by processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-A crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.	+
-		+
-	Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family.,Chandramouli S, Joseph JS, Daudenarde S, Gatchalian J, Cornillez-Ty C, Kuhn P J Virol. 2010 Mar;84(6):3059-67. Epub 2009 Dec 30. PMID:20042502<ref>PMID:20042502</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3lkw" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Nonstructural protein 3D structures\|Nonstructural protein 3D structures]]		*[[Nonstructural protein 3D structures\|Nonstructural protein 3D structures]]
	*[[Virus protease 3D structures\|Virus protease 3D structures]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Den1w~~]]	+	[[Category: Dengue virus 1 Nauru/West Pac/1974]]
		+	[[Category: Dengue virus 1 Singapore/S275/1990]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chandramouli, S]]	+	[[Category: Chandramouli S]]
-	[[Category: Cornillez-Ty, C]]	+	[[Category: Cornillez-Ty C]]
-	[[Category: Daudenarde, S]]	+	[[Category: Daudenarde S]]
-	[[Category: Gatchalian, J]]	+	[[Category: Gatchalian J]]
-	[[Category: Joseph~~, J S~~]]	+	[[Category: Joseph JS]]
-	[[Category: Kuhn, P]]	+	[[Category: Kuhn P]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Ns2b cofactor]]~~	+
-	~~[[Category: Ns3 protease]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Viral protease]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 13:41, 4 May 2022

OCA — Wed, 04 May 2022 13:41:02 GMT

←Older revision		Revision as of 13:41, 4 May 2022
Line 3:		Line 3:
	<StructureSection load='3lkw' size='340' side='right'caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3lkw' size='340' side='right'caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Den1w Den1w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3LKW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Den1w Den1w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3l6p\|3l6p]]</div></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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [~~http~~://pdbe.org/3lkw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw 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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [https://pdbe.org/3lkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [https://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLG_DEN1S POLG_DEN1S]] Protein C: Plays a role in virus budding by binding to 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 in host cytoplasm after hemifusion induced by surface proteins. Can migrate tot cell nucleus where it modulates host functions.[UniProtKB:P17763] 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. Presumably to avoid catastrophic activation of the viral fusion activity in acidic GolGi compartment prior to virion release. prM-E cleavage is ineficient, 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 extodomain. 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 particule 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 ineficient, 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. May play a role in viral genome replication. Assist membrane bending and envelopment of genomic RNA at the endoplasmic reticulum. Excreted as a hexameric lipoparticle that plays a role against host immune responce.[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] Non-structural protein 2B: Required cofactor for the serine protease function of NS3 (By similarity). 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: Induces host endoplasmic regulate the ATPase activity of the NS3 helicase.[UniProtKB:P17763] 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: 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:P17763] RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) 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 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]	+	[[https://www.uniprot.org/uniprot/POLG_DEN1S POLG_DEN1S]] Protein C: Plays a role in virus budding by binding to 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 in host cytoplasm after hemifusion induced by surface proteins. Can migrate tot cell nucleus where it modulates host functions.[UniProtKB:P17763] 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. Presumably to avoid catastrophic activation of the viral fusion activity in acidic GolGi compartment prior to virion release. prM-E cleavage is ineficient, 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 extodomain. 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 particule 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 ineficient, 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. May play a role in viral genome replication. Assist membrane bending and envelopment of genomic RNA at the endoplasmic reticulum. Excreted as a hexameric lipoparticle that plays a role against host immune responce.[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] Non-structural protein 2B: Required cofactor for the serine protease function of NS3 (By similarity). 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: Induces host endoplasmic regulate the ATPase activity of the NS3 helicase.[UniProtKB:P17763] 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: 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:P17763] RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) 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 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 ==
Line 21:		Line 21:

	==See Also==		==See Also==
-	*[[Nonstructural protein\|Nonstructural protein]]	+	*[[Nonstructural protein 3D structures\|Nonstructural protein 3D structures]]
-	*[[Virus protease\|Virus protease]]	+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:37, 28 August 2019

OCA — Wed, 28 Aug 2019 16:37:41 GMT

←Older revision		Revision as of 16:37, 28 August 2019
Line 1:		Line 1:

	==Crystal Structure of Dengue Virus 1 NS2B/NS3 protease active site mutant==		==Crystal Structure of Dengue Virus 1 NS2B/NS3 protease active site mutant==
-	<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='3lkw' size='340' side='right'caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Den1w Den1w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>		<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Den1w Den1w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 3lkw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3lkw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nonstructural protein\|Nonstructural protein]]
		+	*[[Virus protease\|Virus protease]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Den1w]]		[[Category: Den1w]]
		+	[[Category: Large Structures]]
	[[Category: Chandramouli, S]]		[[Category: Chandramouli, S]]
	[[Category: Cornillez-Ty, C]]		[[Category: Cornillez-Ty, C]]

OCA at 08:57, 1 November 2017

OCA — Wed, 01 Nov 2017 08:57:38 GMT

←Older revision		Revision as of 08:57, 1 November 2017
Line 3:		Line 3:
	<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Den1w Den1w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 3lkw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3lkw" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Nonstructural protein\|Nonstructural protein]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Den1w]]
	[[Category: Chandramouli, S]]		[[Category: Chandramouli, S]]
	[[Category: Cornillez-Ty, C]]		[[Category: Cornillez-Ty, C]]

OCA at 11:04, 3 August 2017

OCA — Thu, 03 Aug 2017 11:04:16 GMT

←Older revision		Revision as of 11:04, 3 August 2017
Line 3:		Line 3:
	<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS2B/NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11053 Dengue virus 1])</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://pdbe.org/3lkw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw ProSAT]</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://pdbe.org/3lkw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/~~Q9J7C6_9FLAV Q9J7C6_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~~:~~SAAS026470_004_099774~~]	+	[[http://www.uniprot.org/uniprot/POLG_DEN1S POLG_DEN1S]] Protein C: Plays a role in virus budding by binding to 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 in host cytoplasm after hemifusion induced by surface proteins. Can migrate tot cell nucleus where it modulates host functions.[UniProtKB:P17763] 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. Presumably to avoid catastrophic activation of the viral fusion activity in acidic GolGi compartment prior to virion release. prM-E cleavage is ineficient, 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 extodomain. 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 particule 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 ineficient, 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. May play a role in viral genome replication. Assist membrane bending and envelopment of genomic RNA at the endoplasmic reticulum. Excreted as a hexameric lipoparticle that plays a role against host immune responce.[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] Non-structural protein 2B: Required cofactor for the serine protease function of NS3 (By similarity). 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: Induces host endoplasmic regulate the ATPase activity of the NS3 helicase.[UniProtKB:P17763] 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: 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:P17763] RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) 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 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 ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Dengue virus 1]]
	[[Category: Chandramouli, S]]		[[Category: Chandramouli, S]]
	[[Category: Cornillez-Ty, C]]		[[Category: Cornillez-Ty, C]]

OCA at 20:35, 4 August 2016

OCA — Thu, 04 Aug 2016 20:35:40 GMT

←Older revision		Revision as of 20:35, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Dengue Virus 1 NS2B/NS3 protease active site mutant==		==Crystal Structure of Dengue Virus 1 NS2B/NS3 protease active site mutant==
	<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS2B/NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11053 Dengue virus 1])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS2B/NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11053 Dengue virus 1])</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum]</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://pdbe.org/3lkw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lkw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		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 3lkw" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 12:56, 25 December 2014

OCA — Thu, 25 Dec 2014 12:56:34 GMT

←Older revision		Revision as of 12:56, 25 December 2014
Line 8:		Line 8:
	<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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum]</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q9J7C6_9FLAV Q9J7C6_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:SAAS026470_004_099774]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 09:25, 9 December 2014

OCA — Tue, 09 Dec 2014 09:25:02 GMT

←Older revision		Revision as of 09:25, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3lkw.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal Structure of Dengue Virus 1 NS2B/NS3 protease active site mutant==
		+	<StructureSection load='3lkw' size='340' side='right' caption='[[3lkw]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3lkw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l6p\|3l6p]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS2B/NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11053 Dengue virus 1])</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=3lkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lkw RCSB], [http://www.ebi.ac.uk/pdbsum/3lkw PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication by processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-A crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.

-	~~{{STRUCTURE_3lkw\| PDB=3lkw \| SCENE= }}~~	+	Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family.,Chandramouli S, Joseph JS, Daudenarde S, Gatchalian J, Cornillez-Ty C, Kuhn P J Virol. 2010 Mar;84(6):3059-67. Epub 2009 Dec 30. PMID:20042502<ref>PMID:20042502</ref>

-	~~===Crystal Structure of Dengue Virus 1 NS2B~~/~~NS3 protease active site mutant===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20042502}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3lkw]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Dengue_virus_1 Dengue virus 1]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA].~~	+

	==See Also==		==See Also==
	*[[Nonstructural protein\|Nonstructural protein]]		*[[Nonstructural protein\|Nonstructural protein]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020042502<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Dengue virus 1]]		[[Category: Dengue virus 1]]
-	[[Category: Chandramouli, S.]]	+	[[Category: Chandramouli, S]]
-	[[Category: Cornillez-Ty, C.]]	+	[[Category: Cornillez-Ty, C]]
-	[[Category: Daudenarde, S.]]	+	[[Category: Daudenarde, S]]
-	[[Category: Gatchalian, J.]]	+	[[Category: Gatchalian, J]]
-	[[Category: Joseph, J S.]]	+	[[Category: Joseph, J S]]
-	[[Category: Kuhn, P.]]	+	[[Category: Kuhn, P]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Ns2b cofactor]]		[[Category: Ns2b cofactor]]

OCA at 16:56, 20 October 2012

OCA — Sat, 20 Oct 2012 16:56:08 GMT

←Older revision		Revision as of 16:56, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3lkw]] is a 1 chain structure ~~of [[Nonstructural protein]]~~ with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA].	+	[[3lkw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_1 Dengue virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKW OCA].

	==See Also==		==See Also==

OCA: Protected "3lkw" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 23:17:56 GMT

Protected "3lkw" [edit=sysop:move=sysop]

←Older revision

Revision as of 23:17, 26 July 2012