3txo - Revision history

OCA at 05:49, 13 July 2022

OCA — Wed, 13 Jul 2022 05:49:36 GMT

←Older revision		Revision as of 05:49, 13 July 2022
Line 1:		Line 1:

	==PKC eta kinase in complex with a naphthyridine==		==PKC eta kinase in complex with a naphthyridine==
-	<StructureSection load='3txo' size='340' side='right' caption='[[3txo]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='3txo' size='340' side='right'caption='[[3txo]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TXO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TXO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [~~http~~://pdbe.org/3txo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3txo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3txo 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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [https://pdbe.org/3txo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [https://www.ebi.ac.uk/pdbsum/3txo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3txo ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Disease susceptibility is associated with variations affecting the gene represented in this entry.	+	[[https://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Disease susceptibility is associated with variations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.<ref>PMID:11112424</ref> <ref>PMID:10806212</ref> <ref>PMID:11772428</ref> <ref>PMID:15489897</ref> <ref>PMID:17146445</ref> <ref>PMID:18780722</ref> <ref>PMID:19114660</ref> <ref>PMID:20558593</ref> <ref>PMID:21820409</ref> <ref>PMID:22304920</ref>	+	[[https://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.<ref>PMID:11112424</ref> <ref>PMID:10806212</ref> <ref>PMID:11772428</ref> <ref>PMID:15489897</ref> <ref>PMID:17146445</ref> <ref>PMID:18780722</ref> <ref>PMID:19114660</ref> <ref>PMID:20558593</ref> <ref>PMID:21820409</ref> <ref>PMID:22304920</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==See Also==		==See Also==
-	*[[Protein kinase C\|Protein kinase C]]	+	*[[Protein kinase C 3D structures\|Protein kinase C 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Protein kinase C]]		[[Category: Protein kinase C]]
	[[Category: Cowan-Jacob, S W]]		[[Category: Cowan-Jacob, S W]]

OCA at 19:18, 11 August 2016

OCA — Thu, 11 Aug 2016 19:18:50 GMT

←Older revision		Revision as of 19:18, 11 August 2016
Line 1:		Line 1:
		+
	==PKC eta kinase in complex with a naphthyridine==		==PKC eta kinase in complex with a naphthyridine==
	<StructureSection load='3txo' size='340' side='right' caption='[[3txo]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='3txo' size='340' side='right' caption='[[3txo]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TXO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TXO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [http://www.ebi.ac.uk/pdbsum/3txo 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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [http://pdbe.org/3txo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [http://www.ebi.ac.uk/pdbsum/3txo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3txo ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 3txo" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Protein kinase C]]		[[Category: Protein kinase C]]
	[[Category: Cowan-Jacob, S W]]		[[Category: Cowan-Jacob, S W]]

OCA at 10:56, 4 January 2015

OCA — Sun, 04 Jan 2015 10:56:18 GMT

←Older revision		Revision as of 10:56, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TXO FirstGlance]. <br>		<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TXO FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [http://www.ebi.ac.uk/pdbsum/3txo 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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [http://www.ebi.ac.uk/pdbsum/3txo PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Disease susceptibility is associated with variations affecting the gene represented in this entry.		[[http://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Disease susceptibility is associated with variations affecting the gene represented in this entry.
Line 19:		Line 19:
	2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes.,van Eis MJ, Evenou JP, Floersheim P, Gaul C, Cowan-Jacob SW, Monovich L, Rummel G, Schuler W, Stark W, Strauss A, Matt A, Vangrevelinghe E, Wagner J, Soldermann N Bioorg Med Chem Lett. 2011 Dec 15;21(24):7367-72. Epub 2011 Oct 21. PMID:22078216<ref>PMID:22078216</ref>		2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes.,van Eis MJ, Evenou JP, Floersheim P, Gaul C, Cowan-Jacob SW, Monovich L, Rummel G, Schuler W, Stark W, Strauss A, Matt A, Vangrevelinghe E, Wagner J, Soldermann N Bioorg Med Chem Lett. 2011 Dec 15;21(24):7367-72. Epub 2011 Oct 21. PMID:22078216<ref>PMID:22078216</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>

Line 30:		Line 30:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Protein kinase C]]		[[Category: Protein kinase C]]
-	[[Category: Cowan-Jacob, S W.]]	+	[[Category: Cowan-Jacob, S W]]
-	[[Category: Rummel, G.]]	+	[[Category: Rummel, G]]
-	[[Category: Stark, W.]]	+	[[Category: Stark, W]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Phosphotransferase]]		[[Category: Phosphotransferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:35, 5 June 2014

OCA — Thu, 05 Jun 2014 06:35:06 GMT

←Older revision		Revision as of 06:35, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3txo.~~png~~\|~~left~~\|~~200px~~]]	+	==PKC eta kinase in complex with a naphthyridine==
		+	<StructureSection load='3txo' size='340' side='right' caption='[[3txo]], [[Resolution\|resolution]] 2.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TXO FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07U:2-METHYL-N~1~-[3-(PYRIDIN-4-YL)-2,6-NAPHTHYRIDIN-1-YL]PROPANE-1,2-DIAMINE'>07U</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKCH, PKCL, PRKCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </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=3txo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3txo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3txo RCSB], [http://www.ebi.ac.uk/pdbsum/3txo PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Disease susceptibility is associated with variations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KPCL_HUMAN KPCL_HUMAN]] Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.<ref>PMID:11112424</ref> <ref>PMID:10806212</ref> <ref>PMID:11772428</ref> <ref>PMID:15489897</ref> <ref>PMID:17146445</ref> <ref>PMID:18780722</ref> <ref>PMID:19114660</ref> <ref>PMID:20558593</ref> <ref>PMID:21820409</ref> <ref>PMID:22304920</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The present study describes a novel series of ATP-competitive PKC inhibitors based on the 2,6-naphthyridine template. Example compounds potently inhibit the novel Protein Kinase C (PKC) isotypes delta, epsilon, eta, theta (in particular PKCepsilon/eta, and display a 10-100-fold selectivity over the classical PKC isotypes. The prototype compound 11 was found to inhibit PKCtheta-dependent pathways in vitro and in vivo. In vitro, a-CD3/a-CD28-induced lymphocyte proliferation could be effectively blocked in 10% rat whole blood. In mice, 11 dose-dependently inhibited Staphylococcus aureus enterotoxin B-triggered IL-2 serum levels after oral dosing.

-	<!--	+	2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes.,van Eis MJ, Evenou JP, Floersheim P, Gaul C, Cowan-Jacob SW, Monovich L, Rummel G, Schuler W, Stark W, Strauss A, Matt A, Vangrevelinghe E, Wagner J, Soldermann N Bioorg Med Chem Lett. 2011 Dec 15;21(24):7367-72. Epub 2011 Oct 21. PMID:22078216<ref>PMID:22078216</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3txo"~~, ~~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_3txo\| PDB=3txo \| SCENE= }}~~	+

-	~~===PKC eta kinase in complex with~~ a ~~naphthyridine===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Protein kinase C\|Protein kinase C]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22078216}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22078216 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22078216}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~3txo~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022078216<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Protein kinase C]]		[[Category: Protein kinase C]]

OCA at 07:03, 7 December 2011

OCA — Wed, 07 Dec 2011 07:03:44 GMT

←Older revision		Revision as of 07:03, 7 December 2011
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-	[[Image:3txo.~~jpg~~\|left\|200px]]	+	[[Image:3txo.png\|left\|200px]]

	<!--		<!--

OCA at 06:12, 30 November 2011

OCA — Wed, 30 Nov 2011 06:12:09 GMT

←Older revision		Revision as of 06:12, 30 November 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3txo.jpg\|left\|200px]]

-	The ~~entry 3txo~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3txo", 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_3txo\| PDB=3txo \| SCENE= }}

-	~~Authors: Stark, W., Rummel, G., Cowan-Jacob, S.W.~~	+	===PKC eta kinase in complex with a naphthyridine===

-	~~Description~~: ~~PKC eta~~ kinase in complex ~~with a naphthyridine~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22078216}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22078216 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22078216}}
		+
		+	==About this Structure==
		+	[[3txo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TXO OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022078216</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Protein kinase C]]
		+	[[Category: Cowan-Jacob, S W.]]
		+	[[Category: Rummel, G.]]
		+	[[Category: Stark, W.]]
		+	[[Category: Kinase]]
		+	[[Category: Phosphotransferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

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

OCA — Wed, 05 Oct 2011 06:12:30 GMT

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

←Older revision

Revision as of 06:12, 5 October 2011

OCA: New page: '''Unreleased structure''' The entry 3txo is ON HOLD Authors: Stark, W., Rummel, G., Cowan-Jacob, S.W. Description: PKC eta kinase in complex with a naphthyridine

OCA — Wed, 05 Oct 2011 06:12:29 GMT

New page: '''Unreleased structure''' The entry 3txo is ON HOLD Authors: Stark, W., Rummel, G., Cowan-Jacob, S.W. Description: PKC eta kinase in complex with a naphthyridine

New page

'''Unreleased structure'''

The entry 3txo is ON HOLD

Authors: Stark, W., Rummel, G., Cowan-Jacob, S.W.

Description: PKC eta kinase in complex with a naphthyridine