4hgt - Revision history

OCA at 11:40, 1 March 2024

OCA — Fri, 01 Mar 2024 11:40:47 GMT

←Older revision		Revision as of 11:40, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hgt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hgt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [https://pdbe.org/4hgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [https://www.ebi.ac.uk/pdbsum/4hgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgt 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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [https://pdbe.org/4hgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [https://www.ebi.ac.uk/pdbsum/4hgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgt ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>		[https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1gamma in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1gamma inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms. A single oral dose of compound 13 resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model.
-
-	Structure-Based Design of Potent and Selective CK1gamma Inhibitors.,Huang H, Acquaviva L, Berry V, Bregman H, Chakka N, O'Connor A, DiMauro EF, Dovey J, Epstein O, Grubinska B, Goldstein J, Gunaydin H, Hua Z, Huang X, Huang L, Human J, Long A, Newcomb J, Patel VF, Saffran D, Serafino R, Schneider S, Strathdee C, Tang J, Turci S, White R, Yu V, Zhao H, Wilson C, Martin MW ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64. doi: 10.1021/ml300278f. eCollection, 2012 Dec 13. PMID:24900428<ref>PMID:24900428</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4hgt" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:15, 3 November 2022

OCA — Thu, 03 Nov 2022 08:15:49 GMT

←Older revision		Revision as of 08:15, 3 November 2022
Line 1:		Line 1:

	==Crystal structure of ck1d with compound 13==		==Crystal structure of ck1d with compound 13==
-	<StructureSection load='4hgt' size='340' side='right' caption='[[4hgt]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='4hgt' size='340' side='right'caption='[[4hgt]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hgt]] is a 2 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=4HGT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HGT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hgt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [https://pdbe.org/4hgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [https://www.ebi.ac.uk/pdbsum/4hgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgt ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CSNK1D, HCKID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [~~http~~://pdbe.org/4hgt PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hgt PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgt ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>	+	[https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:

	==See Also==		==See Also==
-	*[[Casein kinase\|Casein kinase]]	+	*[[Casein kinase 3D structures\|Casein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Huang, X~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Ck1d]]~~	+	[[Category: Huang X]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 16:58, 11 August 2016

OCA — Thu, 11 Aug 2016 16:58:52 GMT

←Older revision		Revision as of 16:58, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of ck1d with compound 13==		==Crystal structure of ck1d with compound 13==
	<StructureSection load='4hgt' size='340' side='right' caption='[[4hgt]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='4hgt' size='340' side='right' caption='[[4hgt]], [[Resolution\|resolution]] 1.80Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CSNK1D, HCKID ([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">CSNK1D, HCKID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [http://www.ebi.ac.uk/pdbsum/4hgt 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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [http://pdbe.org/4hgt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [http://www.ebi.ac.uk/pdbsum/4hgt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgt ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4hgt" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 13:46, 4 January 2015

OCA — Sun, 04 Jan 2015 13:46:46 GMT

←Older revision		Revision as of 13:46, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hgt]] is a 2 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=4HGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HGT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hgt]] is a 2 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=4HGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HGT FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CSNK1D, HCKID ([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">CSNK1D, HCKID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [http://www.ebi.ac.uk/pdbsum/4hgt 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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [http://www.ebi.ac.uk/pdbsum/4hgt PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.		[[http://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Huang, X.]]	+	[[Category: Huang, X]]
	[[Category: Ck1d]]		[[Category: Ck1d]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:06, 2 July 2014

OCA — Wed, 02 Jul 2014 06:06:35 GMT

←Older revision		Revision as of 06:06, 2 July 2014
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-	[[~~Image:~~4hgt.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of ck1d with compound 13==
		+	<StructureSection load='4hgt' size='340' side='right' caption='[[4hgt]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hgt]] is a 2 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=4HGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HGT FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15G:2-{2-[(3,4-DIFLUOROPHENOXY)METHYL]-5-METHOXYPYRIDIN-4-YL}-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>15G</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hgl\|4hgl]], [[4hgs\|4hgs]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CSNK1D, HCKID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hgt RCSB], [http://www.ebi.ac.uk/pdbsum/4hgt PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN]] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1gamma in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1gamma inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms. A single oral dose of compound 13 resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model.

-	~~{{STRUCTURE_4hgt\| PDB=4hgt \| SCENE= }}~~	+	Structure-Based Design of Potent and Selective CK1gamma Inhibitors.,Huang H, Acquaviva L, Berry V, Bregman H, Chakka N, O'Connor A, DiMauro EF, Dovey J, Epstein O, Grubinska B, Goldstein J, Gunaydin H, Hua Z, Huang X, Huang L, Human J, Long A, Newcomb J, Patel VF, Saffran D, Serafino R, Schneider S, Strathdee C, Tang J, Turci S, White R, Yu V, Zhao H, Wilson C, Martin MW ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64. doi: 10.1021/ml300278f. eCollection, 2012 Dec 13. PMID:24900428<ref>PMID:24900428</ref>

-	~~===Crystal structure~~ of ~~ck1d with compound 13===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	==~~About this Structure~~==	+	*[[Casein kinase\|Casein kinase]]
-	[[~~4hgt~~]] ~~is a 2 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=4HGT OCA].~~	+	== References ==
-	[[Category: ~~Homo sapiens~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Huang, X.]]		[[Category: Huang, X.]]
	[[Category: Ck1d]]		[[Category: Ck1d]]

OCA at 09:48, 21 November 2012

OCA — Wed, 21 Nov 2012 09:48:39 GMT

←Older revision		Revision as of 09:48, 21 November 2012
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-	~~'''Unreleased structure'''~~	+	[[Image:4hgt.jpg\|left\|200px]]

-	~~The entry~~ 4hgt ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4hgt\| PDB=4hgt \| SCENE= }}

-	~~Authors: Huang, X.~~	+	===Crystal structure of ck1d with compound 13===

-	~~Description: Crystal~~ structure ~~of ck1d~~ with ~~compound 13~~	+
		+	==About this Structure==
		+	[[4hgt]] is a 2 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=4HGT OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Huang, X.]]
		+	[[Category: Ck1d]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 13:21, 8 November 2012

OCA — Thu, 08 Nov 2012 13:21:56 GMT

←Older revision		Revision as of 13:21, 8 November 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4hgt is ON HOLD	+	The entry 4hgt is ON HOLD until Paper Publication

	Authors: Huang, X.		Authors: Huang, X.

	Description: Crystal structure of ck1d with compound 13		Description: Crystal structure of ck1d with compound 13

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

OCA — Wed, 17 Oct 2012 06:37:14 GMT

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

←Older revision

Revision as of 06:37, 17 October 2012

OCA: New page: '''Unreleased structure''' The entry 4hgt is ON HOLD Authors: Huang, X. Description: Crystal structure of ck1d with compound 13

OCA — Wed, 17 Oct 2012 06:37:12 GMT

New page: '''Unreleased structure''' The entry 4hgt is ON HOLD Authors: Huang, X. Description: Crystal structure of ck1d with compound 13

New page

'''Unreleased structure'''

The entry 4hgt is ON HOLD

Authors: Huang, X.

Description: Crystal structure of ck1d with compound 13