3gnw - Revision history

OCA at 15:43, 1 November 2023

OCA — Wed, 01 Nov 2023 15:43:42 GMT

←Older revision		Revision as of 15:43, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='3gnw' size='340' side='right'caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='3gnw' size='340' side='right'caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gnw]] 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=3GNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GNW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gnw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_isolate_HC-J4 Hepatitis C virus isolate HC-J4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GNW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</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]] 2.39Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [https://pdbe.org/3gnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [https://www.ebi.ac.uk/pdbsum/3gnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnw 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [https://pdbe.org/3gnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [https://www.ebi.ac.uk/pdbsum/3gnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POLG_HCVJ4 POLG_HCVJ4]] 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_HCVJ4 POLG_HCVJ4] 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 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hcv~~]]	+	[[Category: Hepatitis C virus isolate HC-J4]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~RNA-directed RNA polymerase]]~~	+	[[Category: De Bondt H]]
-	~~[[Category:~~ Bondt, H De]]	+	[[Category: Nyanguile O]]
-	[[Category: Nyanguile, O]]	+
-	~~[[Category: 5-benzodiazepine]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Capsid protein]]~~	+
-	~~[[Category: Cell membrane]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Envelope protein]]~~	+
-	~~[[Category: Fusion protein]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Helicase]]~~	+
-	~~[[Category: Hepatitis c virus]]~~	+
-	~~[[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: Polymerase]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Ribonucleoprotein]]~~	+
-	~~[[Category: Rna replication]]~~	+
-	~~[[Category: Rna-binding]]~~	+
-	~~[[Category: Rna-directed rna polymerase]]~~	+
-	~~[[Category: Secreted]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Sh3-binding]]~~	+
-	~~[[Category: Sulfone]]~~	+
-	~~[[Category: Thiol protease]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription regulation]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Viral nucleoprotein]]~~	+
-	~~[[Category: Virion~~]]	+

OCA at 07:50, 16 March 2022

OCA — Wed, 16 Mar 2022 07:50:11 GMT

←Older revision		Revision as of 07:50, 16 March 2022
Line 1:		Line 1:

	==HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c==		==HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c==
-	<StructureSection load='3gnw' size='340' side='right' caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>	+	<StructureSection load='3gnw' size='340' side='right'caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gnw]] 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=3GNW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3GNW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gnw]] 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=3GNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GNW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 HCV])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [~~http~~://pdbe.org/3gnw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3gnw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnw 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [https://pdbe.org/3gnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [https://www.ebi.ac.uk/pdbsum/3gnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLG_HCVJ4 POLG_HCVJ4]] 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_HCVJ4 POLG_HCVJ4]] 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 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3gnw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3gnw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Hcv]]		[[Category: Hcv]]
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Bondt, H De]]		[[Category: Bondt, H De]]

OCA at 07:08, 1 November 2017

OCA — Wed, 01 Nov 2017 07:08:27 GMT

←Older revision		Revision as of 07:08, 1 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3gnw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3gnw" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:43, 4 August 2016

OCA — Thu, 04 Aug 2016 11:43:33 GMT

←Older revision		Revision as of 11:43, 4 August 2016
Line 1:		Line 1:
		+
	==HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c==		==HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c==
	<StructureSection load='3gnw' size='340' side='right' caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='3gnw' size='340' side='right' caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gnw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_c_virus_isolate_hc-j4 Hepatitis c virus isolate hc-j4~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GNW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gnw]] 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=3GNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GNW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 ~~Hepatitis C virus isolate HC-J4~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [http://www.ebi.ac.uk/pdbsum/3gnw 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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [http://pdbe.org/3gnw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [http://www.ebi.ac.uk/pdbsum/3gnw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnw 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 3gnw" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hepatitis c virus isolate hc-j4~~]]	+	[[Category: Hcv]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Bondt, H De]]		[[Category: Bondt, H De]]

OCA at 08:58, 25 December 2014

OCA — Thu, 25 Dec 2014 08:58:23 GMT

←Older revision		Revision as of 08:58, 25 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3gnw.~~png~~\|~~left~~\|~~200px~~]]	+	==HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c==
		+	<StructureSection load='3gnw' size='340' side='right' caption='[[3gnw]], [[Resolution\|resolution]] 2.39Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3gnw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_isolate_hc-j4 Hepatitis c virus isolate hc-j4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GNW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=XNC:(11S)-11-[4-(BENZYLOXY)-2-FLUOROPHENYL]-3,3-DIMETHYL-10-[(6-METHYLPYRIDIN-2-YL)CARBONYL]-2,3,4,5,10,11-HEXAHYDROTHIOPYRANO[3,2-B][1,5]BENZODIAZEPIN-6-OL+1,1-DIOXIDE'>XNC</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cso\|3cso]], [[3gnv\|3gnv]], [[3gol\|3gol]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=420174 Hepatitis C virus isolate HC-J4])</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=3gnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gnw RCSB], [http://www.ebi.ac.uk/pdbsum/3gnw PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_HCVJ4 POLG_HCVJ4]] 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 ==
		+	HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.

-	~~{{STRUCTURE_3gnw\| PDB=3gnw \| SCENE= }}~~	+	Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase.,Vandyck K, Cummings MD, Nyanguile O, Boutton CW, Vendeville S, McGowan D, Devogelaere B, Amssoms K, Last S, Rombauts K, Tahri A, Lory P, Hu L, Beauchamp DA, Simmen K, Raboisson P J Med Chem. 2009 Jul 23;52(14):4099-102. PMID:19507864<ref>PMID:19507864</ref>

-	~~===HCV NS5B polymerase in complex with 1~~,~~5 benzodiazepine inhibitor 4c===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19507864}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3gnw]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Hepatitis_c_virus_isolate_hc-j4 Hepatitis c virus isolate hc-j4]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA].~~	+

	==See Also==		==See Also==
	*[[RNA polymerase\|RNA polymerase]]		*[[RNA polymerase\|RNA polymerase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:019507864<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hepatitis c virus isolate hc-j4]]		[[Category: Hepatitis c virus isolate hc-j4]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
-	[[Category: Bondt, H De.]]	+	[[Category: Bondt, H De]]
-	[[Category: Nyanguile, O.]]	+	[[Category: Nyanguile, O]]
	[[Category: 5-benzodiazepine]]		[[Category: 5-benzodiazepine]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]

OCA at 14:52, 20 October 2012

OCA — Sat, 20 Oct 2012 14:52:15 GMT

←Older revision		Revision as of 14:52, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3gnw]] is a 2 chain structure ~~of [[RNA polymerase]]~~ with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_c_virus_isolate~~ Hepatitis c virus isolate]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA].	+	[[3gnw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_isolate_hc-j4 Hepatitis c virus isolate hc-j4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA].

	==See Also==		==See Also==
Line 15:		Line 15:
	==Reference==		==Reference==
	<ref group="xtra">PMID:019507864</ref><references group="xtra"/>		<ref group="xtra">PMID:019507864</ref><references group="xtra"/>
-	[[Category: Hepatitis c virus isolate]]	+	[[Category: Hepatitis c virus isolate hc-j4]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Bondt, H De.]]		[[Category: Bondt, H De.]]

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

OCA — Thu, 26 Jul 2012 16:33:08 GMT

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

←Older revision

Revision as of 16:33, 26 July 2012

OCA at 16:33, 26 July 2012

OCA — Thu, 26 Jul 2012 16:33:05 GMT

←Older revision		Revision as of 16:33, 26 July 2012
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3gnw.png\|left\|200px]]
-	[[Image:3gnw.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3gnw", 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_3gnw\| PDB=3gnw \| SCENE= }}		{{STRUCTURE_3gnw\| PDB=3gnw \| SCENE= }}

	===HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c===		===HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19507864}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19507864 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19507864}}		{{ABSTRACT_PUBMED_19507864}}

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19507864~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019507864</ref><references group="xtra"/>
		+	[[Category: Hepatitis c virus isolate]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
-	[[Category: Viruses]]
	[[Category: Bondt, H De.]]		[[Category: Bondt, H De.]]
	[[Category: Nyanguile, O.]]		[[Category: Nyanguile, O.]]
	[[Category: 5-benzodiazepine]]		[[Category: 5-benzodiazepine]]
-	[[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 61:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[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 Oct 21 10:26:18 2009''

OCA at 08:26, 21 October 2009

OCA — Wed, 21 Oct 2009 08:26:20 GMT

←Older revision		Revision as of 08:26, 21 October 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3gnw.jpg\|left\|200px]]

-	The ~~entry 3gnw~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3gnw", 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_3gnw\| PDB=3gnw \| SCENE= }}

-	~~Authors: Nyanguile~~, ~~O., De Bondt, H.~~	+	===HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c===

-	Description: HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Apr 30 08~~:44:32 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19507864}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19507864 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19507864}}
		+
		+	==About this Structure==
		+	3GNW is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNW OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19507864</ref><references group="xtra"/>
		+	[[Category: RNA-directed RNA polymerase]]
		+	[[Category: Viruses]]
		+	[[Category: Bondt, H De.]]
		+	[[Category: Nyanguile, O.]]
		+	[[Category: 5-benzodiazepine]]
		+	[[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 c virus]]
		+	[[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: Polymerase]]
		+	[[Category: Protease]]
		+	[[Category: Ribonucleoprotein]]
		+	[[Category: Rna replication]]
		+	[[Category: Rna-binding]]
		+	[[Category: Rna-directed rna polymerase]]
		+	[[Category: Secreted]]
		+	[[Category: Serine protease]]
		+	[[Category: Sh3-binding]]
		+	[[Category: Sulfone]]
		+	[[Category: Thiol protease]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription regulation]]
		+	[[Category: Transferase]]
		+	[[Category: Transmembrane]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Viral nucleoprotein]]
		+	[[Category: Virion]]
		+	[[Category: Zinc]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 21 10:26:18 2009''

OCA at 05:44, 30 April 2009

OCA — Thu, 30 Apr 2009 05:44:33 GMT

←Older revision		Revision as of 05:44, 30 April 2009
Line 3:		Line 3:
	The entry 3gnw is ON HOLD until Paper Publication		The entry 3gnw is ON HOLD until Paper Publication

-	Authors: ~~Vandyck, K., Cummings, M.,~~ Nyanguile, O., ~~Boutton, C., Vendeville, S., McGowan, D., Devogelaere, B., Amssoms, K., Last, S., Rombauts, K., Tahri, A., Lory, P., Hu, L., Beauchamp, D., Simmen, K., Raboisson~~, P.	+	Authors: Nyanguile, O., De Bondt, H.

	Description: HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c		Description: HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 4c

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Apr ~~15 09~~:55:21 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 30 08:44:32 2009''