5xqx - Revision history

OCA at 10:19, 27 March 2024

OCA — Wed, 27 Mar 2024 10:19:47 GMT

←Older revision		Revision as of 10:19, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5xqx' size='340' side='right'caption='[[5xqx]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='5xqx' size='340' side='right'caption='[[5xqx]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xqx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5XQX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xqx]] 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=5XQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XQX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CC:N-methyl-4-pyridin-4-yl-1H-pyrrole-2-carboxamide'>8CC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.3Å</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5xqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqx OCA], [~~http~~://pdbe.org/5xqx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xqx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xqx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqx ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CC:N-methyl-4-pyridin-4-yl-1H-pyrrole-2-carboxamide'>8CC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5xqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqx OCA], [https://pdbe.org/5xqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xqx RCSB], [https://www.ebi.ac.uk/pdbsum/5xqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqx 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability.	+
-		+
-	Discovery of potent and selective CDK8 inhibitors through FBDD approach.,Han X, Jiang M, Zhou C, Zhou Z, Xu Z, Wang L, Mayweg AV, Niu R, Jin TG, Yang S Bioorg Med Chem Lett. 2017 Aug 1. pii: S0960-894X(17)30787-4. doi:, 10.1016/j.bmcl.2017.07.080. PMID:28802632<ref>PMID:28802632</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5xqx" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 26:		Line 18:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Xu~~, Z H~~]]	+	[[Category: Xu ZH]]
-	[[Category: Zhou, Z]]	+	[[Category: Zhou Z]]
-	~~[[Category: Cdk8]]~~	+
-	~~[[Category: Cyclin c]]~~	+
-	~~[[Category: Mediator complex]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:57, 14 October 2020

OCA — Wed, 14 Oct 2020 06:57:11 GMT

←Older revision		Revision as of 06:57, 14 October 2020
Line 1:		Line 1:

	==Human CDK8-CYCC in complex with compound 4: N-methyl-4-(4-pyridyl)-1H-pyrrole-2-carboxamide==		==Human CDK8-CYCC in complex with compound 4: N-methyl-4-(4-pyridyl)-1H-pyrrole-2-carboxamide==
-	<StructureSection load='5xqx' size='340' side='right' caption='[[5xqx]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='5xqx' size='340' side='right'caption='[[5xqx]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xqx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQX OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XQX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xqx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XQX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8CC:N-methyl-4-pyridin-4-yl-1H-pyrrole-2-carboxamide'>8CC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CC:N-methyl-4-pyridin-4-yl-1H-pyrrole-2-carboxamide'>8CC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5xqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqx OCA], [http://pdbe.org/5xqx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqx RCSB], [http://www.ebi.ac.uk/pdbsum/5xqx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqx ProSAT]</span></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=5xqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqx OCA], [http://pdbe.org/5xqx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqx RCSB], [http://www.ebi.ac.uk/pdbsum/5xqx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5xqx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5xqx" 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: Large Structures]]
	[[Category: Xu, Z H]]		[[Category: Xu, Z H]]
	[[Category: Zhou, Z]]		[[Category: Zhou, Z]]

OCA: Protected "5xqx" [edit=sysop:move=sysop]

OCA — Wed, 30 Aug 2017 03:58:24 GMT

Protected "5xqx" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:58, 30 August 2017

OCA: New page: ==Human CDK8-CYCC in complex with compound 4: N-methyl-4-(4-pyridyl)-1H-pyrrole-2-carboxamide== == Structural highlights ==
<table><tr><td colspan='2'>[[5xqx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XQX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8CC:N-methyl-4-pyridin-4-yl-1H-pyrrole-2-carboxamide'>8CC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5xqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqx OCA], [http://pdbe.org/5xqx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqx RCSB], [http://www.ebi.ac.uk/pdbsum/5xqx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqx 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>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability.

Discovery of potent and selective CDK8 inhibitors through FBDD approach.,Han X, Jiang M, Zhou C, Zhou Z, Xu Z, Wang L, Mayweg AV, Niu R, Jin TG, Yang S Bioorg Med Chem Lett. 2017 Aug 1. pii: S0960-894X(17)30787-4. doi:, 10.1016/j.bmcl.2017.07.080. PMID:28802632<ref>PMID:28802632</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xqx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Xu, Z H]]
[[Category: Zhou, Z]]
[[Category: Cdk8]]
[[Category: Cyclin c]]
[[Category: Mediator complex]]
[[Category: Transferase]]