3kn2 - Revision history

OCA at 06:34, 19 July 2023

2023-07-19T06:34:40Z

←Older revision		Revision as of 06:34, 19 July 2023
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	<StructureSection load='3kn2' size='340' side='right'caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3kn2' size='340' side='right'caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hepatitis_c_virus_subtype_1a~~ Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_subtype_1b Hepatitis C virus subtype 1b] and [https://en.wikipedia.org/wiki/Hepatitis_C_virus_genotype_1a Hepatitis C virus genotype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-dihydro-1H-inden-2-yl)-2-[({(1S)-2,2-dimethyl-1-[(2-oxopiperidin-1-yl)methyl]propyl}carbamoyl)amino]acetyl}-6,6-dimethyl-N-{(1S)-1-[oxo(prop-2-en-1-ylamino)acetyl]butyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.3Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-dihydro-1H-inden-2-yl)-2-[({(1S)-2,2-dimethyl-1-[(2-oxopiperidin-1-yl)methyl]propyl}carbamoyl)amino]acetyl}-6,6-dimethyl-N-{(1S)-1-[oxo(prop-2-en-1-ylamino)acetyl]butyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [https://pdbe.org/3kn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [https://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [https://pdbe.org/3kn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [https://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_HCV1 POLG_HCV1] Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (PubMed:8533458). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (PubMed:9110985). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (PubMed:9524287). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (PubMed:9811706). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).[UniProtKB:P26662][UniProtKB:P27958][UniProtKB:P29846][UniProtKB:Q99IB8]<ref>PMID:8533458</ref> <ref>PMID:9110985</ref> <ref>PMID:9524287</ref> <ref>PMID:9811706</ref> Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity).[UniProtKB:P27958] Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (PubMed:10390359, PubMed:11152499). 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 (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity).[UniProtKB:P27958]<ref>PMID:10390359</ref> <ref>PMID:11152499</ref> Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity).[UniProtKB:P26662][UniProtKB:P27958][UniProtKB:Q99IB8] Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity).[UniProtKB:P26663][UniProtKB:P27958][UniProtKB:Q99IB8] Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity).[UniProtKB:P27958][UniProtKB:Q9WMX2] The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity).[UniProtKB:P27958][UniProtKB:Q9WMX2] Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity).[UniProtKB:P27958] Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (PubMed:15784895). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (PubMed:9143277). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).[UniProtKB:P26662][UniProtKB:P27958][UniProtKB:Q99IB8][UniProtKB:Q9WMX2]<ref>PMID:15784895</ref> <ref>PMID:9143277</ref> RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.[UniProtKB:P27958]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hepatitis c virus ~~subtype~~ 1a]]	+	[[Category: Hepatitis C virus genotype 1a]]
		+	[[Category: Hepatitis C virus subtype 1b]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bogen, S]]	+	[[Category: Bogen S]]
-	[[Category: Chen~~, K X~~]]	+	[[Category: Chen KX]]
-	[[Category: Nair~~, L G~~]]	+	[[Category: Nair LG]]
-	[[Category: Njoroge, G]]	+	[[Category: Njoroge G]]
-	[[Category: Pinto, P]]	+	[[Category: Pinto P]]
-	[[Category: Prongay, A]]	+	[[Category: Prongay A]]
-	[[Category: Sannigrahi, M]]	+	[[Category: Sannigrahi M]]
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Capsid protein]]~~	+
-	~~[[Category: Envelope protein]]~~	+
-	~~[[Category: Helicase]]~~	+
-	~~[[Category: Hepatitis c virus]]~~	+
-	~~[[Category: Host membrane]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Ketoamide inhibitor]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Ns3 protease domain]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Rna replication]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Virion~~]]	+

OCA at 12:27, 13 October 2021

2021-10-13T12:27:23Z

←Older revision		Revision as of 12:27, 13 October 2021
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	==HCV NS3 Protease Domain with ketoamide inhibitor==		==HCV NS3 Protease Domain with ketoamide inhibitor==
-	<StructureSection load='3kn2' size='340' side='right' caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='3kn2' size='340' side='right'caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-dihydro-1H-inden-2-yl)-2-[({(1S)-2,2-dimethyl-1-[(2-oxopiperidin-1-yl)methyl]propyl}carbamoyl)amino]acetyl}-6,6-dimethyl-N-{(1S)-1-[oxo(prop-2-en-1-ylamino)acetyl]butyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-dihydro-1H-inden-2-yl)-2-[({(1S)-2,2-dimethyl-1-[(2-oxopiperidin-1-yl)methyl]propyl}carbamoyl)amino]acetyl}-6,6-dimethyl-N-{(1S)-1-[oxo(prop-2-en-1-ylamino)acetyl]butyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [~~http~~://pdbe.org/3kn2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [https://pdbe.org/3kn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [https://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 3kn2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3kn2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 22:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Hepatitis c virus subtype 1a]]		[[Category: Hepatitis c virus subtype 1a]]
		+	[[Category: Large Structures]]
	[[Category: Bogen, S]]		[[Category: Bogen, S]]
	[[Category: Chen, K X]]		[[Category: Chen, K X]]

OCA at 09:37, 26 December 2018

2018-12-26T09:37:05Z

←Older revision		Revision as of 09:37, 26 December 2018
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-~~DIHYDRO~~-1H-~~INDEN~~-2-YL)-2-[({(1S)-2,2-~~DIMETHYL~~-1-[(2-~~OXOPIPERIDIN~~-1-YL)~~METHYL~~]~~PROPYL~~}~~CARBAMOYL~~)~~AMINO~~]~~ACETYL~~}-6,6-~~DIMETHYL~~-N-{(1S)-1-[~~OXO~~(~~PROP~~-2-EN-1-~~YLAMINO~~)~~ACETYL~~]~~BUTYL~~}-3-~~AZABICYCLO~~[3.1.0]~~HEXANE~~-2-~~CARBOXAMIDE~~'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-dihydro-1H-inden-2-yl)-2-[({(1S)-2,2-dimethyl-1-[(2-oxopiperidin-1-yl)methyl]propyl}carbamoyl)amino]acetyl}-6,6-dimethyl-N-{(1S)-1-[oxo(prop-2-en-1-ylamino)acetyl]butyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [http://pdbe.org/3kn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [http://pdbe.org/3kn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 ProSAT]</span></td></tr>

OCA at 15:18, 5 August 2016

2016-08-05T15:18:34Z

←Older revision		Revision as of 15:18, 5 August 2016
Line 1:		Line 1:
		+
	==HCV NS3 Protease Domain with ketoamide inhibitor==		==HCV NS3 Protease Domain with ketoamide inhibitor==
	<StructureSection load='3kn2' size='340' side='right' caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3kn2' size='340' side='right' caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-DIHYDRO-1H-INDEN-2-YL)-2-[({(1S)-2,2-DIMETHYL-1-[(2-OXOPIPERIDIN-1-YL)METHYL]PROPYL}CARBAMOYL)AMINO]ACETYL}-6,6-DIMETHYL-N-{(1S)-1-[OXO(PROP-2-EN-1-YLAMINO)ACETYL]BUTYL}-3-AZABICYCLO[3.1.0]HEXANE-2-CARBOXAMIDE'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-DIHYDRO-1H-INDEN-2-YL)-2-[({(1S)-2,2-DIMETHYL-1-[(2-OXOPIPERIDIN-1-YL)METHYL]PROPYL}CARBAMOYL)AMINO]ACETYL}-6,6-DIMETHYL-N-{(1S)-1-[OXO(PROP-2-EN-1-YLAMINO)ACETYL]BUTYL}-3-AZABICYCLO[3.1.0]HEXANE-2-CARBOXAMIDE'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kn2 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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [http://pdbe.org/3kn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn2 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 15:		Line 16:
	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 3kn2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:24, 18 December 2014

2014-12-18T16:24:26Z

←Older revision		Revision as of 16:24, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3kn2\| PDB=3kn2 \| SCENE= }}~~	+	==HCV NS3 Protease Domain with ketoamide inhibitor==
-	===HCV NS3 Protease Domain with ketoamide inhibitor===	+	<StructureSection load='3kn2' size='340' side='right' caption='[[3kn2]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	{{~~ABSTRACT_PUBMED_20004570~~}}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3kn2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KN2 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M66:(1R,2S,5S)-3-{(2S)-2-(2,3-DIHYDRO-1H-INDEN-2-YL)-2-[({(1S)-2,2-DIMETHYL-1-[(2-OXOPIPERIDIN-1-YL)METHYL]PROPYL}CARBAMOYL)AMINO]ACETYL}-6,6-DIMETHYL-N-{(1S)-1-[OXO(PROP-2-EN-1-YLAMINO)ACETYL]BUTYL}-3-AZABICYCLO[3.1.0]HEXANE-2-CARBOXAMIDE'>M66</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</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=3kn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kn2 RCSB], [http://www.ebi.ac.uk/pdbsum/3kn2 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties (Rat AUC (PO)=3.52microMh) compared to 1.

-	~~==About this Structure==~~	+	P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile.,Nair LG, Sannigrahi M, Bogen S, Pinto P, Chen KX, Prongay A, Tong X, Cheng KC, Girijavallabhan V, George Njoroge F Bioorg Med Chem Lett. 2010 Jan 15;20(2):567-70. Epub 2009 Nov 22. PMID:20004570<ref>PMID:20004570</ref>
-	~~[[3kn2]] is a 4 chain structure~~ with ~~sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=3KN2 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:020004570</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Hepatitis c virus subtype 1a]]		[[Category: Hepatitis c virus subtype 1a]]
-	[[Category: Bogen, S.]]	+	[[Category: Bogen, S]]
-	[[Category: Chen, K X.]]	+	[[Category: Chen, K X]]
-	[[Category: Nair, L G.]]	+	[[Category: Nair, L G]]
-	[[Category: Njoroge, G.]]	+	[[Category: Njoroge, G]]
-	[[Category: Pinto, P.]]	+	[[Category: Pinto, P]]
-	[[Category: Prongay, A.]]	+	[[Category: Prongay, A]]
-	[[Category: Sannigrahi, M.]]	+	[[Category: Sannigrahi, M]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Capsid protein]]		[[Category: Capsid protein]]

OCA: Protected "3kn2" [edit=sysop:move=sysop]

2013-04-04T02:30:18Z

Protected "3kn2" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:30, 4 April 2013

OCA at 02:30, 4 April 2013

2013-04-04T02:30:12Z

←Older revision		Revision as of 02:30, 4 April 2013
Line 1:		Line 1:
-	{{Seed}}
-	[[Image:3kn2.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3kn2", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3kn2\| PDB=3kn2 \| SCENE= }}		{{STRUCTURE_3kn2\| PDB=3kn2 \| SCENE= }}
-
	===HCV NS3 Protease Domain with ketoamide inhibitor===		===HCV NS3 Protease Domain with ketoamide inhibitor===
-
-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20004570}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20004570 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20004570}}		{{ABSTRACT_PUBMED_20004570}}

	==About this Structure==		==About this Structure==
-	~~3KN2~~ is a 4 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA].	+	[[3kn2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20004570~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020004570</ref><references group="xtra"/><references/>
	[[Category: Hepatitis c virus subtype 1a]]		[[Category: Hepatitis c virus subtype 1a]]
	[[Category: Bogen, S.]]		[[Category: Bogen, S.]]
Line 47:		Line 31:
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Virion]]		[[Category: Virion]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 3 13:21:09 2010''

OCA at 11:21, 3 March 2010

2010-03-03T11:21:10Z

←Older revision		Revision as of 11:21, 3 March 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3kn2.~~jpg~~\|left\|200px]]	+	[[Image:3kn2.png\|left\|200px]]

	<!--		<!--
Line 48:		Line 48:
	[[Category: Virion]]		[[Category: Virion]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Jan 20 16~~:01:44 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 3 13:21:09 2010''

OCA at 14:01, 20 January 2010

2010-01-20T14:01:45Z

←Older revision		Revision as of 14:01, 20 January 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3kn2.jpg\|left\|200px]]

-	The ~~entry 3kn2~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3kn2", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3kn2\| PDB=3kn2 \| SCENE= }}

-	~~Authors: Nair, L.G., Sannigrahi, M., Pinto, P., Bogen, S., Chen, K.X., Njoroge, G., Prongay, A.~~	+	===HCV NS3 Protease Domain with ketoamide inhibitor===

-	Description: HCV NS3 Protease Domain with ketoamide inhibitor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan ~~13 13~~:32:28 2010''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20004570}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20004570 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20004570}}
		+
		+	==About this Structure==
		+	3KN2 is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN2 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20004570</ref><references group="xtra"/>
		+	[[Category: Hepatitis c virus subtype 1a]]
		+	[[Category: Bogen, S.]]
		+	[[Category: Chen, K X.]]
		+	[[Category: Nair, L G.]]
		+	[[Category: Njoroge, G.]]
		+	[[Category: Pinto, P.]]
		+	[[Category: Prongay, A.]]
		+	[[Category: Sannigrahi, M.]]
		+	[[Category: Atp-binding]]
		+	[[Category: Capsid protein]]
		+	[[Category: Envelope protein]]
		+	[[Category: Helicase]]
		+	[[Category: Hepatitis c virus]]
		+	[[Category: Host membrane]]
		+	[[Category: Hydrolase]]
		+	[[Category: Ketoamide inhibitor]]
		+	[[Category: Membrane]]
		+	[[Category: Ns3 protease domain]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Rna replication]]
		+	[[Category: Serine protease]]
		+	[[Category: Transmembrane]]
		+	[[Category: Virion]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 20 16:01:44 2010''

OCA at 11:32, 13 January 2010

2010-01-13T11:32:28Z

←Older revision		Revision as of 11:32, 13 January 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3kn2 is ON HOLD ~~until sometime in the future~~	+	The entry 3kn2 is ON HOLD

-	Authors: ~~Latha G~~ Nair~~; Mousumi~~ Sannigrahi~~; Patrick~~ Pinto~~; Stephane~~ Bogen~~; Kevin X~~ Chen~~; George~~ Njoroge~~; Andrew~~ Prongay;	+	Authors: Nair, L.G., Sannigrahi, M., Pinto, P., Bogen, S., Chen, K.X., Njoroge, G., Prongay, A.

	Description: HCV NS3 Protease Domain with ketoamide inhibitor		Description: HCV NS3 Protease Domain with ketoamide inhibitor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Nov 25 09:~~13:~~29 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 13 13:32:28 2010''