6gzm - Revision history

OCA at 10:34, 5 September 2018

OCA — Wed, 05 Sep 2018 10:34:24 GMT

←Older revision		Revision as of 10:34, 5 September 2018
Line 3:		Line 3:
	<StructureSection load='6gzm' size='340' side='right' caption='[[6gzm]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='6gzm' size='340' side='right' caption='[[6gzm]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gzm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GZM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gzm]] 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=6GZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GZM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LCI:[4-[[4-[5-(cyclopropylmethyl)-1-methyl-pyrazol-4-yl]-5-fluoranyl-pyrimidin-2-yl]amino]cyclohexyl]azanium'>LCI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LCI:[4-[[4-[5-(cyclopropylmethyl)-1-methyl-pyrazol-4-yl]-5-fluoranyl-pyrimidin-2-yl]amino]cyclohexyl]azanium'>LCI</scene></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=6gzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gzm OCA], [http://pdbe.org/6gzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gzm RCSB], [http://www.ebi.ac.uk/pdbsum/6gzm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gzm 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=6gzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gzm OCA], [http://pdbe.org/6gzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gzm RCSB], [http://www.ebi.ac.uk/pdbsum/6gzm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gzm ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== 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>		[[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 ==
		+	CKIalpha ablation induces p53 activation, and CKIalpha degradation underlies the therapeutic effect of lenalidomide in a pre-leukemia syndrome. Here we describe the development of CKIalpha inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIalpha-induced p53 activation and its anti-leukemic activity. Oncogene-driving super-enhancers (SEs) are highly sensitive to CDK7/9 inhibition. We identified multiple newly gained SEs in primary mouse acute myeloid leukemia (AML) cells and demonstrate that the inhibitors abolish many SEs and preferentially suppress the transcription elongation of SE-driven oncogenes. We show that blocking CKIalpha together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Leukemia progenitors are selectively eliminated by the inhibitors, explaining their therapeutic efficacy with preserved hematopoiesis and leukemia cure potential; they eradicate leukemia in MLL-AF9 and Tet2(-/-);Flt3(ITD) AML mouse models and in several patient-derived AML xenograft models, supporting their potential efficacy in curing human leukemia.
		+
		+	Small Molecules Co-targeting CKIalpha and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models.,Minzel W, Venkatachalam A, Fink A, Hung E, Brachya G, Burstain I, Shaham M, Rivlin A, Omer I, Zinger A, Elias S, Winter E, Erdman PE, Sullivan RW, Fung L, Mercurio F, Li D, Vacca J, Kaushansky N, Shlush L, Oren M, Levine R, Pikarsky E, Snir-Alkalay I, Ben-Neriah Y Cell. 2018 Aug 20. pii: S0092-8674(18)30973-5. doi: 10.1016/j.cell.2018.07.045. PMID:30146162<ref>PMID:30146162</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gzm" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Ben-neriah, Y]]		[[Category: Ben-neriah, Y]]
	[[Category: Fink, A]]		[[Category: Fink, A]]

OCA at 07:34, 29 August 2018

OCA — Wed, 29 Aug 2018 07:34:43 GMT

←Older revision		Revision as of 07:34, 29 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gzm ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of Human CKIdelta with A86==
-		+	<StructureSection load='6gzm' size='340' side='right' caption='[[6gzm]], [[Resolution\|resolution]] 1.59Å' scene=''>
-	~~Authors~~: ~~Ben~~-~~neriah, Y~~., ~~Venkatachalam~~, A., ~~Minzel~~, W., ~~Fink~~, A., ~~Snir~~-~~Alkalay~~, I., ~~Vacca~~, J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gzm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GZM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GZM FirstGlance]. <br>
-	~~Description: Crystal Structure of Human CKIdelta with A86~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LCI:[4-[[4-[5-(cyclopropylmethyl)-1-methyl-pyrazol-4-yl]-5-fluoranyl-pyrimidin-2-yl]amino]cyclohexyl]azanium'>LCI</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=6gzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gzm OCA], [http://pdbe.org/6gzm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gzm RCSB], [http://www.ebi.ac.uk/pdbsum/6gzm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gzm ProSAT]</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ben-neriah, Y]]
	[[Category: Fink, A]]		[[Category: Fink, A]]
-	[[Category: ~~Ben-Neriah~~, Y]]	+	[[Category: Minzel, W]]
	[[Category: Snir-Alkalay, I]]		[[Category: Snir-Alkalay, I]]
-	[[Category: Minzel, W]]
	[[Category: Vacca, J]]		[[Category: Vacca, J]]
	[[Category: Venkatachalam, A]]		[[Category: Venkatachalam, A]]
		+	[[Category: A86]]
		+	[[Category: Cdk9]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Transferase]]

OCA at 17:12, 1 August 2018

OCA — Wed, 01 Aug 2018 17:12:06 GMT

←Older revision		Revision as of 17:12, 1 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6gzm is ON HOLD	+	The entry 6gzm is ON HOLD until Paper Publication

	Authors: Ben-neriah, Y., Venkatachalam, A., Minzel, W., Fink, A., Snir-Alkalay, I., Vacca, J.		Authors: Ben-neriah, Y., Venkatachalam, A., Minzel, W., Fink, A., Snir-Alkalay, I., Vacca, J.

-	Description: Crystal Structure of Human ~~CDK9/cyclinT1~~ with A86	+	Description: Crystal Structure of Human CKIdelta with A86
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Fink, A]]		[[Category: Fink, A]]

OCA: Protected "6gzm" [edit=sysop:move=sysop]

OCA — Wed, 11 Jul 2018 04:19:30 GMT

Protected "6gzm" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:19, 11 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gzm is ON HOLD Authors: Ben-neriah, Y., Venkatachalam, A., Minzel, W., Fink, A., Snir-Alkalay, I., Vacca, J. Description: Crystal Structure of Hum...

OCA — Wed, 11 Jul 2018 04:19:28 GMT

New page: '''Unreleased structure''' The entry 6gzm is ON HOLD Authors: Ben-neriah, Y., Venkatachalam, A., Minzel, W., Fink, A., Snir-Alkalay, I., Vacca, J. Description: Crystal Structure of Hum...

New page

'''Unreleased structure'''

The entry 6gzm is ON HOLD

Authors: Ben-neriah, Y., Venkatachalam, A., Minzel, W., Fink, A., Snir-Alkalay, I., Vacca, J.

Description: Crystal Structure of Human CDK9/cyclinT1 with A86
[[Category: Unreleased Structures]]
[[Category: Fink, A]]
[[Category: Ben-Neriah, Y]]
[[Category: Snir-Alkalay, I]]
[[Category: Minzel, W]]
[[Category: Vacca, J]]
[[Category: Venkatachalam, A]]