4wtl - Revision history

OCA at 07:36, 27 September 2023

OCA — Wed, 27 Sep 2023 07:36:47 GMT

←Older revision		Revision as of 07:36, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_JFH-1 Hepatitis C virus JFH-1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_JFH-1 Hepatitis C virus JFH-1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [https://pdbe.org/4wtl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [https://www.ebi.ac.uk/pdbsum/4wtl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtl 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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [https://pdbe.org/4wtl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [https://www.ebi.ac.uk/pdbsum/4wtl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtl ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:26, 7 April 2023

OCA — Fri, 07 Apr 2023 07:26:12 GMT

←Older revision		Revision as of 07:26, 7 April 2023
Line 3:		Line 3:
	<StructureSection load='4wtl' size='340' side='right'caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4wtl' size='340' side='right'caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Hcv Hcv~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4WTL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_JFH-1 Hepatitis C virus JFH-1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WTL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [https://pdbe.org/4wtl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [https://www.ebi.ac.uk/pdbsum/4wtl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtl 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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [~~http~~://pdbe.org/4wtl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4wtl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtl ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POLG_HCVJF POLG_HCVJF]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).	+	[https://www.uniprot.org/uniprot/POLG_HCVJF POLG_HCVJF] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hcv~~]]	+	[[Category: Hepatitis C virus JFH-1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~RNA-directed RNA polymerase~~]]	+	[[Category: Synthetic construct]]
-	[[Category: Appleby~~, T C~~]]	+	[[Category: Appleby TC]]
-	[[Category: Edwards~~, T E]]~~	+	[[Category: Edwards TE]]
-	~~[[Category: Ns5b]]~~	+
-	~~[[Category: Primed initiation]]~~	+
-	~~[[Category: Primer]]~~	+
-	~~[[Category: Rdrp]]~~	+
-	~~[[Category: Resistance mutation]]~~	+
-	~~[[Category: Template]]~~	+
-	~~[[Category: Transferase-rna complex]]~~	+
-	~~[[Category: Viral~~]]	+

OCA at 07:55, 4 March 2020

OCA — Wed, 04 Mar 2020 07:55:26 GMT

←Older revision		Revision as of 07:55, 4 March 2020
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF HCV NS5B GENOTYPE 2A JFH-1 ISOLATE WITH S15G E86Q E87Q C223H V321I MUTATIONS IN COMPLEX WITH RNA TEMPLATE 5'-UACC, RNA PRIMER 5'-PGG, MN2+, AND UDP==		==CRYSTAL STRUCTURE OF HCV NS5B GENOTYPE 2A JFH-1 ISOLATE WITH S15G E86Q E87Q C223H V321I MUTATIONS IN COMPLEX WITH RNA TEMPLATE 5'-UACC, RNA PRIMER 5'-PGG, MN2+, AND UDP==
-	<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4wtl' size='340' side='right'caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcv Hcv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTL FirstGlance]. <br>		<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcv Hcv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTL FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4wtl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4wtl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Hcv]]		[[Category: Hcv]]
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Appleby, T C]]		[[Category: Appleby, T C]]

OCA at 12:14, 6 November 2017

OCA — Mon, 06 Nov 2017 12:14:08 GMT

←Older revision		Revision as of 12:14, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcv Hcv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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='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>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4wtl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4wtl" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hcv]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Appleby, T C]]		[[Category: Appleby, T C]]
	[[Category: Edwards, T E]]		[[Category: Edwards, T E]]
-	[[Category: Hcv]]
	[[Category: Ns5b]]		[[Category: Ns5b]]
	[[Category: Primed initiation]]		[[Category: Primed initiation]]

OCA at 00:21, 26 January 2017

OCA — Thu, 26 Jan 2017 00:21:26 GMT

←Older revision		Revision as of 00:21, 26 January 2017
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF HCV NS5B GENOTYPE 2A JFH-1 ISOLATE WITH S15G E86Q E87Q C223H V321I MUTATIONS IN COMPLEX WITH RNA TEMPLATE 5'-UACC, RNA PRIMER 5'-PGG, MN2+, AND UDP==		==CRYSTAL STRUCTURE OF HCV NS5B GENOTYPE 2A JFH-1 ISOLATE WITH S15G E86Q E87Q C223H V321I MUTATIONS IN COMPLEX WITH RNA TEMPLATE 5'-UACC, RNA PRIMER 5'-PGG, MN2+, AND UDP==
	<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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='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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [http://www.ebi.ac.uk/pdbsum/4wtl 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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [http://pdbe.org/4wtl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [http://www.ebi.ac.uk/pdbsum/4wtl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wtl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4wtl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:12, 25 February 2015

OCA — Wed, 25 Feb 2015 08:12:30 GMT

←Older revision		Revision as of 08:12, 25 February 2015
Line 9:		Line 9:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/POLG_HCVJF POLG_HCVJF]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).		[[http://www.uniprot.org/uniprot/POLG_HCVJF POLG_HCVJF]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A beta loop and a C-terminal membrane-anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3' terminus, and vacate the active-site cavity during elongation. We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site.
		+
		+	Viral replication. Structural basis for RNA replication by the hepatitis C virus polymerase.,Appleby TC, Perry JK, Murakami E, Barauskas O, Feng J, Cho A, Fox D 3rd, Wetmore DR, McGrath ME, Ray AS, Sofia MJ, Swaminathan S, Edwards TE Science. 2015 Feb 13;347(6223):771-5. doi: 10.1126/science.1259210. PMID:25678663<ref>PMID:25678663</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 12:04, 12 February 2015

OCA — Thu, 12 Feb 2015 12:04:37 GMT

←Older revision		Revision as of 12:04, 12 February 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==CRYSTAL STRUCTURE OF HCV NS5B GENOTYPE 2A JFH-1 ISOLATE WITH S15G E86Q E87Q C223H V321I MUTATIONS IN COMPLEX WITH RNA TEMPLATE 5'-UACC, RNA PRIMER 5'-PGG, MN2+, AND UDP==
-		+	<StructureSection load='4wtl' size='340' side='right' caption='[[4wtl]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~The entry~~ 4wtl is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4wtl]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WTL FirstGlance]. <br>
-	~~Authors~~: ~~Edwards~~, T.E., ~~Appleby~~, T.C.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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>
-	~~Description~~:	+	<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=4wtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wtl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wtl RCSB], [http://www.ebi.ac.uk/pdbsum/4wtl PDBsum]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: Edwards, T.E]]	+	== Function ==
-	[[Category: ~~Appleby, T.C~~]]	+	[[http://www.uniprot.org/uniprot/POLG_HCVJF POLG_HCVJF]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).
		+	__TOC__
		+	</StructureSection>
		+	[[Category: RNA-directed RNA polymerase]]
		+	[[Category: Appleby, T C]]
		+	[[Category: Edwards, T E]]
		+	[[Category: Hcv]]
		+	[[Category: Ns5b]]
		+	[[Category: Primed initiation]]
		+	[[Category: Primer]]
		+	[[Category: Rdrp]]
		+	[[Category: Resistance mutation]]
		+	[[Category: Template]]
		+	[[Category: Transferase-rna complex]]
		+	[[Category: Viral]]

OCA at 19:58, 24 December 2014

OCA — Wed, 24 Dec 2014 19:58:00 GMT

←Older revision		Revision as of 19:58, 24 December 2014
Line 5:		Line 5:
	Authors: Edwards, T.E., Appleby, T.C.		Authors: Edwards, T.E., Appleby, T.C.

-	Description:	+	Description:
		+	[[Category: Unreleased Structures]]
		+	[[Category: Edwards, T.E]]
		+	[[Category: Appleby, T.C]]

OCA at 11:57, 19 November 2014

OCA — Wed, 19 Nov 2014 11:57:26 GMT

←Older revision		Revision as of 11:57, 19 November 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4wtl is ON HOLD	+	The entry 4wtl is ON HOLD until Paper Publication

	Authors: Edwards, T.E., Appleby, T.C.		Authors: Edwards, T.E., Appleby, T.C.

	Description:		Description:

OCA: Protected "4wtl" [edit=sysop:move=sysop]

OCA — Wed, 05 Nov 2014 08:09:02 GMT

Protected "4wtl" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:09, 5 November 2014