View source for 8p73


==Cryo-EM structure of CAK in complex with inhibitor ICEC0829==
<StructureSection load='8p73' size='340' side='right'caption='[[8p73]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8p73]] is a 3 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=8P73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P73 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=X50:(3R,4R)-4-[[[7-[(phenylmethyl)amino]-3-propan-2-yl-pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidine-3,4-diol'>X50</scene>, <scene name='pdbligand=X58:(3S,4S)-4-[[[7-[(phenylmethyl)amino]-3-propan-2-yl-pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidine-3,4-diol'>X58</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=8p73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p73 OCA], [https://pdbe.org/8p73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p73 RCSB], [https://www.ebi.ac.uk/pdbsum/8p73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p73 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDK7_HUMAN CDK7_HUMAN] Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.<ref>PMID:9372954</ref> <ref>PMID:9840937</ref> <ref>PMID:10024882</ref> <ref>PMID:11113184</ref> <ref>PMID:16327805</ref> <ref>PMID:17386261</ref> <ref>PMID:17373709</ref> <ref>PMID:17901130</ref> <ref>PMID:19450536</ref> <ref>PMID:19015234</ref> <ref>PMID:19667075</ref> <ref>PMID:19136461</ref> <ref>PMID:19071173</ref> <ref>PMID:20360007</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ali S]]
[[Category: Bahl AK]]
[[Category: Cushing VI]]
[[Category: Feng J]]
[[Category: Greber BJ]]
[[Category: Jurgaityte K]]
[[Category: Koh AF]]
[[Category: Kotecha A]]