6qtj - Revision history

OCA at 12:08, 24 January 2024

OCA — Wed, 24 Jan 2024 12:08:21 GMT

←Older revision		Revision as of 12:08, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qtj' size='340' side='right'caption='[[6qtj]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='6qtj' size='340' side='right'caption='[[6qtj]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qtj]] 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=6QTJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QTJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qtj]] 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=6QTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QTJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JHK:~{N},~{N}-dimethyl-2-[4-[4-(2,6-naphthyridin-4-yl)phenyl]pyrazol-1-yl]ethanamide'>JHK</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]] 2.48Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JHK:~{N},~{N}-dimethyl-2-[4-[4-(2,6-naphthyridin-4-yl)phenyl]pyrazol-1-yl]ethanamide'>JHK</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6qtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtj OCA], [~~http~~://pdbe.org/6qtj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qtj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qtj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtj 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=6qtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtj OCA], [https://pdbe.org/6qtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qtj RCSB], [https://www.ebi.ac.uk/pdbsum/6qtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CDK8_HUMAN CDK8_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.<ref>PMID:10993082</ref> <ref>PMID:15546612</ref> [[http://www.uniprot.org/uniprot/CCNC_HUMAN CCNC_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex.<ref>PMID:8700522</ref> <ref>PMID:16595664</ref>	+	[https://www.uniprot.org/uniprot/CDK8_HUMAN CDK8_HUMAN] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.<ref>PMID:10993082</ref> <ref>PMID:15546612</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6qtj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qtj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cyclin 3D structures\|Cyclin 3D structures]]
		+	*[[Cyclin-dependent kinase 3D structures\|Cyclin-dependent kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Boettcher, J]]	+	[[Category: Boettcher J]]
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor~~]]	+

OCA at 06:05, 22 April 2020

OCA — Wed, 22 Apr 2020 06:05:03 GMT

←Older revision		Revision as of 06:05, 22 April 2020
Line 3:		Line 3:
	<StructureSection load='6qtj' size='340' side='right'caption='[[6qtj]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='6qtj' size='340' side='right'caption='[[6qtj]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qtj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTJ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QTJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qtj]] 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=6QTJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QTJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JHK:~{N},~{N}-dimethyl-2-[4-[4-(2,6-naphthyridin-4-yl)phenyl]pyrazol-1-yl]ethanamide'>JHK</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JHK:~{N},~{N}-dimethyl-2-[4-[4-(2,6-naphthyridin-4-yl)phenyl]pyrazol-1-yl]ethanamide'>JHK</scene></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=6qtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtj OCA], [http://pdbe.org/6qtj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qtj RCSB], [http://www.ebi.ac.uk/pdbsum/6qtj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtj ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNC ([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://proteopedia.org/fgij/fg.htm?mol=6qtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtj OCA], [http://pdbe.org/6qtj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qtj RCSB], [http://www.ebi.ac.uk/pdbsum/6qtj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/CDK8_HUMAN CDK8_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.<ref>PMID:10993082</ref> <ref>PMID:15546612</ref> [[http://www.uniprot.org/uniprot/CCNC_HUMAN CCNC_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex.<ref>PMID:8700522</ref> <ref>PMID:16595664</ref>		[[http://www.uniprot.org/uniprot/CDK8_HUMAN CDK8_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.<ref>PMID:10993082</ref> <ref>PMID:15546612</ref> [[http://www.uniprot.org/uniprot/CCNC_HUMAN CCNC_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex.<ref>PMID:8700522</ref> <ref>PMID:16595664</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Natural killer (NK) cells play a pivotal role in controlling cancer. Multiple extracellular receptors and internal signaling nodes tightly regulate NK activation. Cyclin-dependent kinases of the mediator complex (CDK8 and CDK19) were described as a signaling intermediates in NK cells. Here, we report for the first time the development and use of CDK8/19 inhibitors to suppress phosphorylation of STAT1(S727) in NK cells and to augment the production of the cytolytic molecules perforin and granzyme B (GZMB). Functionally, this resulted in enhanced NK-cell-mediated lysis of primary leukemia cells. Treatment with the CDK8/19 inhibitor BI-1347 increased the response rate and survival of mice bearing melanoma and breast cancer xenografts. In addition, CDK8/19 inhibition augmented the antitumoral activity of anti-PD-1 antibody and SMAC mimetic therapy, both agents that promote T-cell-mediated antitumor immunity. Treatment with the SMAC mimetic compound BI-8382 resulted in an increased number of NK cells infiltrating EMT6 tumors. Combination of the CDK8/19 inhibitor BI-1347, which augments the amount of degranulation enzymes, with the SMAC mimetic BI-8382 resulted in increased survival of mice carrying the EMT6 breast cancer model. The observed survival benefit was dependent on an intermittent treatment schedule of BI-1347, suggesting the importance of circumventing a hyporesponsive state of NK cells. These results suggest that CDK8/19 inhibitors can be combined with modulators of the adaptive immune system to inhibit the growth of solid tumors, independent of their activity on cancer cells, but rather through promoting NK-cell function.
		+
		+	Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance.,Hofmann MH, Mani R, Engelhardt H, Impagnatiello MA, Carotta S, Kerenyi M, Lorenzo-Herrero S, Bottcher J, Scharn D, Arnhof H, Zoephel A, Schnitzer R, Gerstberger T, Sanderson MP, Rajgolikar G, Goswami S, Vasu S, Ettmayer P, Gonzalez S, Pearson M, McConnell DB, Kraut N, Muthusamy N, Moll J Mol Cancer Ther. 2020 Apr;19(4):1018-1030. doi: 10.1158/1535-7163.MCT-19-0789., Epub 2020 Feb 5. PMID:32024684<ref>PMID:32024684</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qtj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Boettcher, J]]		[[Category: Boettcher, J]]

OCA at 09:48, 18 March 2020

OCA — Wed, 18 Mar 2020 09:48:04 GMT

←Older revision		Revision as of 09:48, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qtj is ~~ON HOLD~~	+	==Crystal structure of human CDK8/CYCC in complex with BI 919811==
-		+	<StructureSection load='6qtj' size='340' side='right'caption='[[6qtj]], [[Resolution\|resolution]] 2.48Å' scene=''>
-	~~Authors~~: ~~Boettcher~~, J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qtj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QTJ FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~human CDK8~~/~~CYCC~~ in complex with ~~BI 919811~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JHK:~{N},~{N}-dimethyl-2-[4-[4-(2,6-naphthyridin-4-yl)phenyl]pyrazol-1-yl]ethanamide'>JHK</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=6qtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qtj OCA], [http://pdbe.org/6qtj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qtj RCSB], [http://www.ebi.ac.uk/pdbsum/6qtj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qtj ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CDK8_HUMAN CDK8_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.<ref>PMID:10993082</ref> <ref>PMID:15546612</ref> [[http://www.uniprot.org/uniprot/CCNC_HUMAN CCNC_HUMAN]] Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex.<ref>PMID:8700522</ref> <ref>PMID:16595664</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Boettcher, J]]		[[Category: Boettcher, J]]
		+	[[Category: Cell cycle]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]

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

OCA — Wed, 06 Mar 2019 05:53:10 GMT

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

←Older revision

Revision as of 05:53, 6 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qtj is ON HOLD Authors: Boettcher, J. Description: Crystal structure of human CDK8/CYCC in complex with BI 919811 [[Category: Unreleased Structure...

OCA — Wed, 06 Mar 2019 05:53:08 GMT

New page: '''Unreleased structure''' The entry 6qtj is ON HOLD Authors: Boettcher, J. Description: Crystal structure of human CDK8/CYCC in complex with BI 919811 [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 6qtj is ON HOLD

Authors: Boettcher, J.

Description: Crystal structure of human CDK8/CYCC in complex with BI 919811
[[Category: Unreleased Structures]]
[[Category: Boettcher, J]]