6xd3: Difference between revisions
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The | ==Structure of the human CAK in complex with THZ1== | ||
<StructureSection load='6xd3' size='340' side='right'caption='[[6xd3]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6xd3]] 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=6XD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XD3 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]] 3.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=V0G:~{N}-[3-[[5-chloranyl-4-(1~{H}-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[4-(dimethylamino)butanoylamino]benzamide'>V0G</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=6xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xd3 OCA], [https://pdbe.org/6xd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xd3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xd3 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds. | |||
The cryoelectron microscopy structure of the human CDK-activating kinase.,Greber BJ, Perez-Bertoldi JM, Lim K, Iavarone AT, Toso DB, Nogales E Proc Natl Acad Sci U S A. 2020 Aug 27. pii: 2009627117. doi:, 10.1073/pnas.2009627117. PMID:32855301<ref>PMID:32855301</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6xd3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclin 3D structures|Cyclin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Greber BJ]] | |||
[[Category: Iavarone AT]] | |||
[[Category: Lim K]] | |||
[[Category: Nogales E]] | |||
[[Category: Perez-Bertoldi JM]] | |||
[[Category: Toso DB]] | |||
Latest revision as of 11:28, 17 October 2024
Structure of the human CAK in complex with THZ1Structure of the human CAK in complex with THZ1
Structural highlights
Publication Abstract from PubMedThe human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds. The cryoelectron microscopy structure of the human CDK-activating kinase.,Greber BJ, Perez-Bertoldi JM, Lim K, Iavarone AT, Toso DB, Nogales E Proc Natl Acad Sci U S A. 2020 Aug 27. pii: 2009627117. doi:, 10.1073/pnas.2009627117. PMID:32855301[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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