1c2p - Revision history

OCA at 15:38, 13 March 2024

OCA — Wed, 13 Mar 2024 15:38:11 GMT

←Older revision		Revision as of 15:38, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='1c2p' size='340' side='right'caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1c2p' size='340' side='right'caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~9hepc 9hepc~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C2P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C2P FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 1.9Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [https://pdbe.org/1c2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [https://www.ebi.ac.uk/pdbsum/1c2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2p 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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [https://pdbe.org/1c2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [https://www.ebi.ac.uk/pdbsum/1c2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2p 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c2p ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c2p ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Various classes of nucleotidyl polymerases with different transcriptional roles contain a conserved core structure. Less is known, however, about the distinguishing features of these enzymes, particularly those of the RNA-dependent RNA polymerase class. The 1. 9 A resolution crystal structure of hepatitis C virus (HCV) nonstructural protein 5B (NS5B) presented here provides the first complete and detailed view of an RNA-dependent RNA polymerase. While canonical polymerase features exist in the structure, NS5B adopts a unique shape due to extensive interactions between the fingers and thumb polymerase subdomains that serve to encircle the enzyme active site. Several insertions in the fingers subdomain account for intersubdomain linkages that include two extended loops and a pair of antiparallel alpha-helices. The HCV NS5B apoenzyme structure reported here can accommodate a template:primer duplex without global conformational changes, supporting the hypothesis that this structure is essentially preserved during the reaction pathway. This NS5B template:primer model also allows identification of a new structural motif involved in stabilizing the nascent base pair.
-
-	Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site.,Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC Nat Struct Biol. 1999 Oct;6(10):937-43. PMID:10504728<ref>PMID:10504728</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1c2p" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hepacivirus C]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed RNA polymerase]]~~	+	[[Category: Cable MB]]
-	[[Category: Cable~~, M B~~]]	+	[[Category: Ferrari E]]
-	[[Category: Ferrari, E]]	+	[[Category: Hong Z]]
-	[[Category: Hong, Z]]	+	[[Category: Lesburg CA]]
-	[[Category: Lesburg~~, C A~~]]	+	[[Category: Mannarino AF]]
-	[[Category: Mannarino~~, A F~~]]	+	[[Category: Weber PC]]
-	[[Category: Weber~~, P C]]~~	+
-	~~[[Category: Polymerase rna-dependent rna polymerase hepatitis c virus ns5b apoenzyme]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:28, 11 August 2021

OCA — Wed, 11 Aug 2021 06:28:09 GMT

←Older revision		Revision as of 06:28, 11 August 2021
Line 3:		Line 3:
	<StructureSection load='1c2p' size='340' side='right'caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1c2p' size='340' side='right'caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1C2P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C2P FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [~~http~~://pdbe.org/1c2p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1c2p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2p 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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [https://pdbe.org/1c2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [https://www.ebi.ac.uk/pdbsum/1c2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2p 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 31:

	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:47, 6 November 2019

OCA — Wed, 06 Nov 2019 09:47:35 GMT

←Older revision		Revision as of 09:47, 6 November 2019
Line 1:		Line 1:

	==HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE==		==HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE==
-	<StructureSection load='1c2p' size='340' side='right' caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='1c2p' size='340' side='right'caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C2P FirstGlance]. <br>		<table><tr><td colspan='2'>[[1c2p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C2P FirstGlance]. <br>
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1c2p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1c2p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Cable, M B]]		[[Category: Cable, M B]]

OCA at 06:08, 31 January 2018

OCA — Wed, 31 Jan 2018 06:08:12 GMT

←Older revision		Revision as of 06:08, 31 January 2018
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c2/1c2p_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c2/1c2p_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 10:59, 8 November 2017

OCA — Wed, 08 Nov 2017 10:59:41 GMT

←Older revision		Revision as of 10:59, 8 November 2017
Line 1:		Line 1:
		+
	==HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE==		==HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE==
	<StructureSection load='1c2p' size='340' side='right' caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='1c2p' size='340' side='right' caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://pdbe.org/1c2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p 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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://pdbe.org/1c2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1c2p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1c2p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1c2p" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:57, 7 February 2016

OCA — Sun, 07 Feb 2016 05:57:30 GMT

←Older revision		Revision as of 05:57, 7 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c2p ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 22:31, 9 September 2015

OCA — Wed, 09 Sep 2015 22:31:02 GMT

←Older revision

Revision as of 22:31, 9 September 2015

OCA at 08:26, 24 December 2014

OCA — Wed, 24 Dec 2014 08:26:01 GMT

←Older revision		Revision as of 08:26, 24 December 2014
Line 7:		Line 7:
	<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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p 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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 10:26, 22 December 2014

OCA — Mon, 22 Dec 2014 10:26:45 GMT

←Older revision		Revision as of 10:26, 22 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1c2p]] 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=1C2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C2P FirstGlance]. <br>		<table><tr><td colspan='2'>[[1c2p]] 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=1C2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C2P FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p 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=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
-	[[Category: Cable, M B.]]	+	[[Category: Cable, M B]]
-	[[Category: Ferrari, E.]]	+	[[Category: Ferrari, E]]
-	[[Category: Hong, Z.]]	+	[[Category: Hong, Z]]
-	[[Category: Lesburg, C A.]]	+	[[Category: Lesburg, C A]]
-	[[Category: Mannarino, A F.]]	+	[[Category: Mannarino, A F]]
-	[[Category: Weber, P C.]]	+	[[Category: Weber, P C]]
	[[Category: Polymerase rna-dependent rna polymerase hepatitis c virus ns5b apoenzyme]]		[[Category: Polymerase rna-dependent rna polymerase hepatitis c virus ns5b apoenzyme]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 17:14, 20 August 2014

OCA — Wed, 20 Aug 2014 17:14:47 GMT

←Older revision		Revision as of 17:14, 20 August 2014
Line 1:		Line 1:
-	[[~~Image~~:1c2p.~~png\|left~~\|200px]]	+	==HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE==
		+	<StructureSection load='1c2p' size='340' side='right' caption='[[1c2p]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1c2p]] 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=1C2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C2P FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c2p RCSB], [http://www.ebi.ac.uk/pdbsum/1c2p PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c2/1c2p_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Various classes of nucleotidyl polymerases with different transcriptional roles contain a conserved core structure. Less is known, however, about the distinguishing features of these enzymes, particularly those of the RNA-dependent RNA polymerase class. The 1. 9 A resolution crystal structure of hepatitis C virus (HCV) nonstructural protein 5B (NS5B) presented here provides the first complete and detailed view of an RNA-dependent RNA polymerase. While canonical polymerase features exist in the structure, NS5B adopts a unique shape due to extensive interactions between the fingers and thumb polymerase subdomains that serve to encircle the enzyme active site. Several insertions in the fingers subdomain account for intersubdomain linkages that include two extended loops and a pair of antiparallel alpha-helices. The HCV NS5B apoenzyme structure reported here can accommodate a template:primer duplex without global conformational changes, supporting the hypothesis that this structure is essentially preserved during the reaction pathway. This NS5B template:primer model also allows identification of a new structural motif involved in stabilizing the nascent base pair.

-	~~{{STRUCTURE_1c2p\| PDB=1c2p \| SCENE= }}~~	+	Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site.,Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC Nat Struct Biol. 1999 Oct;6(10):937-43. PMID:10504728<ref>PMID:10504728</ref>

-	~~===HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_10504728}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1c2p]] 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=1C2P OCA].~~	+

	==See Also==		==See Also==
	*[[RNA polymerase\|RNA polymerase]]		*[[RNA polymerase\|RNA polymerase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:010504728<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]