5hvy
From Proteopedia
(Difference between revisions)
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=66X:N-{(3S)-1-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRROLIDIN-3-YL}-N-{4-[(MORPHOLIN-4-YL)METHYL]-3-(TRIFLUOROMETHYL)PHENYL}UREA'>66X</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=66X:N-{(3S)-1-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRROLIDIN-3-YL}-N-{4-[(MORPHOLIN-4-YL)METHYL]-3-(TRIFLUOROMETHYL)PHENYL}UREA'>66X</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cei|5cei]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cei|5cei]]</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=5hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hvy OCA], [http://pdbe.org/5hvy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hvy RCSB], [http://www.ebi.ac.uk/pdbsum/5hvy 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=5hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hvy OCA], [http://pdbe.org/5hvy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hvy RCSB], [http://www.ebi.ac.uk/pdbsum/5hvy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hvy 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 == | ||
| + | Using Sorafenib as a starting point, a series of potent and selective inhibitors of CDK8 was developed. When cocrystallized with CDK8 and cyclin C, these compounds exhibit a Type-II (DMG-out) binding mode. | ||
| + | |||
| + | Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8.,Bergeron P, Koehler MF, Blackwood EM, Bowman K, Clark K, Firestein R, Kiefer JR, Maskos K, McCleland ML, Orren L, Ramaswamy S, Salphati L, Schmidt S, Schneider EV, Wu J, Beresini M ACS Med Chem Lett. 2016 Apr 5;7(6):595-600. doi: 10.1021/acsmedchemlett.6b00044. , eCollection 2016 Jun 9. PMID:27326333<ref>PMID:27326333</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5hvy" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 18:13, 12 July 2016
CDK8/CYCC IN COMPLEX WITH COMPOUND 20
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