4b6f - Revision history

OCA at 11:44, 20 December 2023

2023-12-20T11:44:21Z

←Older revision		Revision as of 11:44, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='4b6f' size='340' side='right'caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='4b6f' size='340' side='right'caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4b6f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B6F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4b6f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_(isolate_BK) Hepatitis C virus (isolate BK)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B6F FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=20L:(4~~-~~PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>~~, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.89Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[1a1q\|1a1q]]~~, [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [https://pdbe.org/4b6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [https://www.ebi.ac.uk/pdbsum/4b6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6f 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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [https://pdbe.org/4b6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [https://www.ebi.ac.uk/pdbsum/4b6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6f ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>	+	[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Carr~~, M G~~]]	+	[[Category: Carr MG]]
-	[[Category: Chessari, G]]	+	[[Category: Chessari G]]
-	[[Category: Coyle, J]]	+	[[Category: Coyle J]]
-	[[Category: Graham, B]]	+	[[Category: Graham B]]
-	[[Category: Hiscock~~, S D~~]]	+	[[Category: Hiscock SD]]
-	[[Category: Jhoti, H]]	+	[[Category: Jhoti H]]
-	[[Category: Murray~~, C W~~]]	+	[[Category: Murray CW]]
-	[[Category: Pathuri, P]]	+	[[Category: Pathuri P]]
-	[[Category: Rich~~, S J~~]]	+	[[Category: Rich SJ]]
-	[[Category: Richardson~~, C J~~]]	+	[[Category: Richardson CJ]]
-	[[Category: Saalau-Bethell~~, S M~~]]	+	[[Category: Saalau-Bethell SM]]
-	[[Category: Williams~~, P A~~]]	+	[[Category: Williams PA]]
-	[[Category: Woodhead~~, A J]]~~	+	[[Category: Woodhead AJ]]
-	~~[[Category: Allosteric pocket]]~~	+
-	~~[[Category: Fusion protein]]~~	+
-	~~[[Category: Helicase-protease]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 07:01, 31 August 2022

2022-08-31T07:01:24Z

←Older revision		Revision as of 07:01, 31 August 2022
Line 3:		Line 3:
	<StructureSection load='4b6f' size='340' side='right'caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='4b6f' size='340' side='right'caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4b6f]] 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=4B6F OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4B6F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4b6f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B6F FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1q\|1a1q]], [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a1q\|1a1q]], [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [~~http~~://pdbe.org/4b6f PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4b6f PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6f 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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [https://pdbe.org/4b6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [https://www.ebi.ac.uk/pdbsum/4b6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6f ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>	+	[[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4b6f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4b6f" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hcv]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Carr, M G]]		[[Category: Carr, M G]]

OCA at 13:44, 13 March 2019

2019-03-13T13:44:31Z

←Older revision		Revision as of 13:44, 13 March 2019
Line 1:		Line 1:

	==Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function==		==Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function==
-	<StructureSection load='4b6f' size='340' side='right' caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>	+	<StructureSection load='4b6f' size='340' side='right'caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4b6f]] 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=4B6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6F FirstGlance]. <br>		<table><tr><td colspan='2'>[[4b6f]] 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=4B6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6F FirstGlance]. <br>
Line 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Hcv]]		[[Category: Hcv]]
		+	[[Category: Large Structures]]
	[[Category: Carr, M G]]		[[Category: Carr, M G]]
	[[Category: Chessari, G]]		[[Category: Chessari, G]]

OCA at 21:54, 5 August 2016

2016-08-05T21:54:19Z

←Older revision		Revision as of 21:54, 5 August 2016
Line 1:		Line 1:
		+
	==Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function==		==Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function==
	<StructureSection load='4b6f' size='340' side='right' caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='4b6f' size='340' side='right' caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4b6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_c_virus_(isolate_bk) Hepatitis c virus (isolate bk)~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4b6f]] 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=4B6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6F FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1q\|1a1q]], [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1q\|1a1q]], [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [http://www.ebi.ac.uk/pdbsum/4b6f 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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [http://pdbe.org/4b6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [http://www.ebi.ac.uk/pdbsum/4b6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6f ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4b6f" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hcv]]
	[[Category: Carr, M G]]		[[Category: Carr, M G]]
	[[Category: Chessari, G]]		[[Category: Chessari, G]]

OCA at 22:14, 25 December 2014

2014-12-25T22:14:00Z

←Older revision		Revision as of 22:14, 25 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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [http://www.ebi.ac.uk/pdbsum/4b6f 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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [http://www.ebi.ac.uk/pdbsum/4b6f PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:54, 9 December 2014

2014-12-09T15:54:58Z

←Older revision		Revision as of 15:54, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4b6f.~~png~~\|~~left~~\|~~200px~~]]	+	==Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function==
		+	<StructureSection load='4b6f' size='340' side='right' caption='[[4b6f]], [[Resolution\|resolution]] 2.89Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4b6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_(isolate_bk) Hepatitis c virus (isolate bk)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B6F FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20L:(4-PHENOXYPHENYL)METHYLAZANIUM'>20L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1a1q\|1a1q]], [[1bt7\|1bt7]], [[1c2p\|1c2p]], [[1csj\|1csj]], [[1cu1\|1cu1]], [[1gx5\|1gx5]], [[1gx6\|1gx6]], [[1jxp\|1jxp]], [[1nhu\|1nhu]], [[1nhv\|1nhv]], [[1ns3\|1ns3]], [[1os5\|1os5]], [[1quv\|1quv]], [[2awz\|2awz]], [[2ax0\|2ax0]], [[2ax1\|2ax1]], [[2brk\|2brk]], [[2brl\|2brl]], [[2i1r\|2i1r]], [[2jc0\|2jc0]], [[2jc1\|2jc1]], [[2wcx\|2wcx]], [[2who\|2who]], [[2xwy\|2xwy]], [[4a92\|4a92]], [[4b6e\|4b6e]], [[8ohm\|8ohm]]</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=4b6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b6f RCSB], [http://www.ebi.ac.uk/pdbsum/4b6f PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Here we report a highly conserved new binding site located at the interface between the protease and helicase domains of the hepatitis C virus (HCV) NS3 protein. Using a chemical lead, identified by fragment screening and structure-guided design, we demonstrate that this site has a regulatory function on the protease activity via an allosteric mechanism. We propose that compounds binding at this allosteric site inhibit the function of the NS3 protein by stabilizing an inactive conformation and thus represent a new class of direct-acting antiviral agents.

-	~~{{STRUCTURE_4b6f\| PDB=4b6f \| SCENE= }}~~	+	Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function.,Saalau-Bethell SM, Woodhead AJ, Chessari G, Carr MG, Coyle J, Graham B, Hiscock SD, Murray CW, Pathuri P, Rich SJ, Richardson CJ, Williams PA, Jhoti H Nat Chem Biol. 2012 Sep 30. doi: 10.1038/nchembio.1081. PMID:23023261<ref>PMID:23023261</ref>

-	~~===Discovery~~ of ~~an allosteric mechanism for~~ the ~~regulation~~ of ~~HCV NS3 protein function===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_23023261}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[4b6f]] is a 2 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Hepatitis_c_virus_(isolate_bk) Hepatitis c virus (isolate bk)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA].~~	+	</StructureSection>
-	[[Category: Carr, M G.]]	+	[[Category: Carr, M G]]
-	[[Category: Chessari, G.]]	+	[[Category: Chessari, G]]
-	[[Category: Coyle, J.]]	+	[[Category: Coyle, J]]
-	[[Category: Graham, B.]]	+	[[Category: Graham, B]]
-	[[Category: Hiscock, S D.]]	+	[[Category: Hiscock, S D]]
-	[[Category: Jhoti, H.]]	+	[[Category: Jhoti, H]]
-	[[Category: Murray, C W.]]	+	[[Category: Murray, C W]]
-	[[Category: Pathuri, P.]]	+	[[Category: Pathuri, P]]
-	[[Category: Rich, S J.]]	+	[[Category: Rich, S J]]
-	[[Category: Richardson, C J.]]	+	[[Category: Richardson, C J]]
-	[[Category: Saalau-Bethell, S M.]]	+	[[Category: Saalau-Bethell, S M]]
-	[[Category: Williams, P A.]]	+	[[Category: Williams, P A]]
-	[[Category: Woodhead, A J.]]	+	[[Category: Woodhead, A J]]
	[[Category: Allosteric pocket]]		[[Category: Allosteric pocket]]
	[[Category: Fusion protein]]		[[Category: Fusion protein]]
	[[Category: Helicase-protease]]		[[Category: Helicase-protease]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 06:14, 17 October 2012

2012-10-17T06:14:52Z

←Older revision		Revision as of 06:14, 17 October 2012
Line 1:		Line 1:
-	[[Image:4b6f.~~jpg~~\|left\|200px]]	+	[[Image:4b6f.png\|left\|200px]]

	{{STRUCTURE_4b6f\| PDB=4b6f \| SCENE= }}		{{STRUCTURE_4b6f\| PDB=4b6f \| SCENE= }}
Line 5:		Line 5:
	===Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function===		===Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function===

		+	{{ABSTRACT_PUBMED_23023261}}

	==About this Structure==		==About this Structure==
-	[[4b6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Viruses Viruses~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA].	+	[[4b6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_(isolate_bk) Hepatitis c virus (isolate bk)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA].
-	~~[[Category: Viruses]]~~	+
	[[Category: Carr, M G.]]		[[Category: Carr, M G.]]
	[[Category: Chessari, G.]]		[[Category: Chessari, G.]]

OCA at 06:23, 3 October 2012

2012-10-03T06:23:36Z

←Older revision		Revision as of 06:23, 3 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4b6f.jpg\|left\|200px]]

-	~~The entry~~ 4b6f ~~is ON HOLD~~	+	{{STRUCTURE_4b6f\| PDB=4b6f \| SCENE= }}

-	~~Authors: Saalau-Bethell, S.M., Woodhead, A.J., Chessari, G., Carr, M.G., Coyle, J., Graham, B., Hiscock, S.D., Murray, C.W., Pathuri, P., Rich, S.J., Richardson, C.J., Williams, P.A., Jhoti, H.~~	+	===Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function===

-	~~Description~~: ~~Discovery of an allosteric mechanism for the regulation of HCV NS3~~ protein ~~function~~	+
		+	==About this Structure==
		+	[[4b6f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B6F OCA].
		+	[[Category: Viruses]]
		+	[[Category: Carr, M G.]]
		+	[[Category: Chessari, G.]]
		+	[[Category: Coyle, J.]]
		+	[[Category: Graham, B.]]
		+	[[Category: Hiscock, S D.]]
		+	[[Category: Jhoti, H.]]
		+	[[Category: Murray, C W.]]
		+	[[Category: Pathuri, P.]]
		+	[[Category: Rich, S J.]]
		+	[[Category: Richardson, C J.]]
		+	[[Category: Saalau-Bethell, S M.]]
		+	[[Category: Williams, P A.]]
		+	[[Category: Woodhead, A J.]]
		+	[[Category: Allosteric pocket]]
		+	[[Category: Fusion protein]]
		+	[[Category: Helicase-protease]]
		+	[[Category: Hydrolase]]

OCA at 05:22, 22 August 2012

2012-08-22T05:22:06Z

←Older revision		Revision as of 05:22, 22 August 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4b6f is ON HOLD ~~until sometime in the future~~	+	The entry 4b6f is ON HOLD

	Authors: Saalau-Bethell, S.M., Woodhead, A.J., Chessari, G., Carr, M.G., Coyle, J., Graham, B., Hiscock, S.D., Murray, C.W., Pathuri, P., Rich, S.J., Richardson, C.J., Williams, P.A., Jhoti, H.		Authors: Saalau-Bethell, S.M., Woodhead, A.J., Chessari, G., Carr, M.G., Coyle, J., Graham, B., Hiscock, S.D., Murray, C.W., Pathuri, P., Rich, S.J., Richardson, C.J., Williams, P.A., Jhoti, H.

	Description: Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function		Description: Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function

OCA: Protected "4b6f" [edit=sysop:move=sysop]

2012-08-15T05:13:22Z

Protected "4b6f" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 15 August 2012