3g86 - Revision history

OCA at 07:01, 6 September 2023

OCA — Wed, 06 Sep 2023 07:01:54 GMT

←Older revision		Revision as of 07:01, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3g86' size='340' side='right'caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3g86' size='340' side='right'caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3g86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hcv Hcv~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G86 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3g86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_(isolate_BK) Hepatitis C virus (isolate BK)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G86 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.2Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11105 HCV])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [https://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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [https://pdbe.org/3g86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [https://www.ebi.ac.uk/pdbsum/3g86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g86 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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [https://pdbe.org/3g86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [https://www.ebi.ac.uk/pdbsum/3g86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g86 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>	+	[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hcv]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed RNA polymerase]]~~	+	[[Category: Ghate M]]
-	[[Category: Ghate, M]]	+	[[Category: Harris SF]]
-	[[Category: Harris~~, S F]]~~	+
-	~~[[Category: Acetylation]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Capsid protein]]~~	+
-	~~[[Category: Cell membrane]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Envelope protein]]~~	+
-	~~[[Category: Fusion protein]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Helicase]]~~	+
-	~~[[Category: Hepatitis]]~~	+
-	~~[[Category: Host-virus interaction]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Interferon antiviral system evasion]]~~	+
-	~~[[Category: Lipid droplet]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Mitochondrion]]~~	+
-	~~[[Category: Multifunctional enzyme]]~~	+
-	~~[[Category: Ns5b]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Nucleotidyltransferase]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Oncogene]]~~	+
-	~~[[Category: Palmitate]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Ribonucleoprotein]]~~	+
-	~~[[Category: Rna replication]]~~	+
-	~~[[Category: Rna-binding]]~~	+
-	~~[[Category: Rna-directed rna polymerase]]~~	+
-	~~[[Category: Secreted]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Sh3-binding]]~~	+
-	~~[[Category: Thiol protease]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription regulation]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase rna-dependent rna polymerase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Ubl conjugation]]~~	+
-	~~[[Category: Viral nucleoprotein]]~~	+
-	~~[[Category: Virion]]~~	+
-	~~[[Category: Zinc~~]]	+

OCA at 07:58, 9 March 2022

OCA — Wed, 09 Mar 2022 07:58:08 GMT

←Older revision		Revision as of 07:58, 9 March 2022
Line 1:		Line 1:

	==Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor==		==Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor==
-	<StructureSection load='3g86' size='340' side='right' caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='3g86' size='340' side='right'caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3g86]] is a 2 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=3G86 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3G86 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3g86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hcv Hcv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G86 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11105 HCV])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11105 HCV])</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'>[https://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [https://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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [~~http~~://pdbe.org/3g86 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3g86 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3g86 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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [https://pdbe.org/3g86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [https://www.ebi.ac.uk/pdbsum/3g86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g86 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>	+	[[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Hcv]]		[[Category: Hcv]]
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Ghate, M]]		[[Category: Ghate, M]]

OCA at 07:26, 5 December 2018

OCA — Wed, 05 Dec 2018 07:26:26 GMT

←Older revision		Revision as of 07:26, 5 December 2018
Line 32:		Line 32:
	[[Category: Ghate, M]]		[[Category: Ghate, M]]
	[[Category: Harris, S F]]		[[Category: Harris, S F]]
		+	[[Category: Acetylation]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Capsid protein]]		[[Category: Capsid protein]]
	[[Category: Cell membrane]]		[[Category: Cell membrane]]
		+	[[Category: Cytoplasm]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
	[[Category: Envelope protein]]		[[Category: Envelope protein]]
Line 72:		Line 74:
	[[Category: Transferase rna-dependent rna polymerase]]		[[Category: Transferase rna-dependent rna polymerase]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
		+	[[Category: Ubl conjugation]]
	[[Category: Viral nucleoprotein]]		[[Category: Viral nucleoprotein]]
	[[Category: Virion]]		[[Category: Virion]]
		+	[[Category: Zinc]]

OCA at 22:54, 4 August 2016

OCA — Thu, 04 Aug 2016 22:54:24 GMT

←Older revision		Revision as of 22:54, 4 August 2016
Line 1:		Line 1:
		+
	==Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor==		==Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor==
	<StructureSection load='3g86' size='340' side='right' caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3g86' size='340' side='right' caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3g86]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_c_virus Hepatitis c virus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G86 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3g86]] is a 2 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=3G86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G86 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~11103 Hepatitis C virus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11105 HCV])</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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [http://www.ebi.ac.uk/pdbsum/3g86 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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [http://pdbe.org/3g86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [http://www.ebi.ac.uk/pdbsum/3g86 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3g86 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3g86" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hepatitis c virus~~]]	+	[[Category: Hcv]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Ghate, M]]		[[Category: Ghate, M]]
Line 38:		Line 40:
	[[Category: Fusion protein]]		[[Category: Fusion protein]]
	[[Category: Glycoprotein]]		[[Category: Glycoprotein]]
-	[[Category: Hcv]]
	[[Category: Helicase]]		[[Category: Helicase]]
	[[Category: Hepatitis]]		[[Category: Hepatitis]]

OCA at 13:47, 25 December 2014

OCA — Thu, 25 Dec 2014 13:47:01 GMT

←Older revision		Revision as of 13:47, 25 December 2014
Line 9:		Line 9:
	<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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [http://www.ebi.ac.uk/pdbsum/3g86 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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [http://www.ebi.ac.uk/pdbsum/3g86 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:15, 3 December 2014

OCA — Wed, 03 Dec 2014 10:15:04 GMT

←Older revision		Revision as of 10:15, 3 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3g86.~~png~~\|~~left~~\|~~200px~~]]	+	==Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor==
		+	<StructureSection load='3g86' size='340' side='right' caption='[[3g86]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3g86]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G86 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=T18:N-{3-[6-FLUORO-1-(4-FLUOROBENZYL)-4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL]-1,1-DIOXIDO-4H-1,4-BENZOTHIAZIN-7-YL}METHANESULFONAMIDE'>T18</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2giq\|2giq]], [[3h59\|3h59]], [[3h5s\|3h5s]], [[3h5u\|3h5u]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 Hepatitis C virus])</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=3g86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g86 RCSB], [http://www.ebi.ac.uk/pdbsum/3g86 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.

-	~~{{STRUCTURE_3g86\| PDB=3g86 \| SCENE= }}~~	+	Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure-activity relationships of benzothiazine-substituted quinolinediones.,de Vicente J, Hendricks RT, Smith DB, Fell JB, Fischer J, Spencer SR, Stengel PJ, Mohr P, Robinson JE, Blake JF, Hilgenkamp RK, Yee C, Adjabeng G, Elworthy TR, Tracy J, Chin E, Li J, Wang B, Bamberg JT, Stephenson R, Oshiro C, Harris SF, Ghate M, Leveque V, Najera I, Le Pogam S, Rajyaguru S, Ao-Ieong G, Alexandrova L, Larrabee S, Brandl M, Briggs A, Sukhtankar S, Farrell R, Xu B Bioorg Med Chem Lett. 2009 Jul 1;19(13):3642-6. Epub 2009 May 7. PMID:19457662<ref>PMID:19457662</ref>

-	~~===Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19457662}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3g86]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Hepatitis_c_virus Hepatitis c virus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].~~	+

	==See Also==		==See Also==
	*[[RNA polymerase\|RNA polymerase]]		*[[RNA polymerase\|RNA polymerase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:019457662<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
-	[[Category: Ghate, M.]]	+	[[Category: Ghate, M]]
-	[[Category: Harris, S F.]]	+	[[Category: Harris, S F]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]

OCA at 17:25, 20 October 2012

OCA — Sat, 20 Oct 2012 17:25:41 GMT

←Older revision		Revision as of 17:25, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3g86]] is a 2 chain structure ~~of [[RNA polymerase]]~~ with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].	+	[[3g86]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].

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

OCA: Protected "3g86" [edit=sysop:move=sysop]

OCA — Fri, 27 Jul 2012 00:51:24 GMT

Protected "3g86" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:51, 27 July 2012

OCA at 00:51, 27 July 2012

OCA — Fri, 27 Jul 2012 00:51:22 GMT

←Older revision		Revision as of 00:51, 27 July 2012
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3g86.png\|left\|200px]]
-	[[Image:3g86.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3g86", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3g86\| PDB=3g86 \| SCENE= }}		{{STRUCTURE_3g86\| PDB=3g86 \| SCENE= }}

	===Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor===		===Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19457662}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19457662 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19457662}}		{{ABSTRACT_PUBMED_19457662}}

	==About this Structure==		==About this Structure==
-	~~3G86~~ is a 2 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].	+	[[3g86]] is a 2 chain structure of [[RNA polymerase]] with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19457662~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019457662</ref><references group="xtra"/>
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Ghate, M.]]		[[Category: Ghate, M.]]
	[[Category: Harris, S F.]]		[[Category: Harris, S F.]]
-	[[Category: Acetylation]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Capsid protein]]		[[Category: Capsid protein]]
	[[Category: Cell membrane]]		[[Category: Cell membrane]]
-	[[Category: Cytoplasm]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
	[[Category: Envelope protein]]		[[Category: Envelope protein]]
Line 71:		Line 60:
	[[Category: Transferase rna-dependent rna polymerase]]		[[Category: Transferase rna-dependent rna polymerase]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
-	[[Category: Ubl conjugation]]
	[[Category: Viral nucleoprotein]]		[[Category: Viral nucleoprotein]]
	[[Category: Virion]]		[[Category: Virion]]
-	[[Category: Zinc]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 9 09:31:28 2009''

OCA at 06:31, 9 September 2009

OCA — Wed, 09 Sep 2009 06:31:30 GMT

←Older revision		Revision as of 06:31, 9 September 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3g86.jpg\|left\|200px]]

-	The ~~entry 3g86~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3g86", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3g86\| PDB=3g86 \| SCENE= }}

-	~~Authors: Harris, S.F., Ghate, M.~~	+	===Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor===

-	Description: Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Mar 11 11~~:10:55 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19457662}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19457662 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19457662}}
		+
		+	==About this Structure==
		+	3G86 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G86 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19457662</ref><references group="xtra"/>
		+	[[Category: Hepatitis c virus]]
		+	[[Category: RNA-directed RNA polymerase]]
		+	[[Category: Ghate, M.]]
		+	[[Category: Harris, S F.]]
		+	[[Category: Acetylation]]
		+	[[Category: Apoptosis]]
		+	[[Category: Atp-binding]]
		+	[[Category: Capsid protein]]
		+	[[Category: Cell membrane]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Envelope protein]]
		+	[[Category: Fusion protein]]
		+	[[Category: Glycoprotein]]
		+	[[Category: Hcv]]
		+	[[Category: Helicase]]
		+	[[Category: Hepatitis]]
		+	[[Category: Host-virus interaction]]
		+	[[Category: Hydrolase]]
		+	[[Category: Interferon antiviral system evasion]]
		+	[[Category: Lipid droplet]]
		+	[[Category: Lipoprotein]]
		+	[[Category: Membrane]]
		+	[[Category: Metal-binding]]
		+	[[Category: Mitochondrion]]
		+	[[Category: Multifunctional enzyme]]
		+	[[Category: Ns5b]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Nucleotidyltransferase]]
		+	[[Category: Nucleus]]
		+	[[Category: Oncogene]]
		+	[[Category: Palmitate]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Protease]]
		+	[[Category: Ribonucleoprotein]]
		+	[[Category: Rna replication]]
		+	[[Category: Rna-binding]]
		+	[[Category: Rna-directed rna polymerase]]
		+	[[Category: Secreted]]
		+	[[Category: Serine protease]]
		+	[[Category: Sh3-binding]]
		+	[[Category: Thiol protease]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription regulation]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase rna-dependent rna polymerase]]
		+	[[Category: Transmembrane]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Viral nucleoprotein]]
		+	[[Category: Virion]]
		+	[[Category: Zinc]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 9 09:31:28 2009''