Dataset
Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package
- Documentation:
- A description of the materials and methods is included within the TEP datasheet. Cyclin-dependent kinase 12 (CDK12) phosphorylates RNA Pol II C-terminal domain (CTD) to promote transcriptional elongation of large DNA damage response genes. CDK12 is frequently mutated or amplified in cancer and its loss sensitises cells to DNA damage. Here we present 3 crystal structures of the human CDK12/CycK complex including apo, AMP-PNP and covalent inhibitor complexes. Kinase assays compare domain truncations and report the Km values for substrate. THZ531 is presented as a potent and selective inhibitor of CDK12 with nanomolar activity in leukemic cell lines.
- Version:
- 3
Actions
Authors
Contributors
+ Bullock, AN
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Principal Investigator (PI)
+ Dixon-Clarke, S
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Researcher
+ Elkins, J
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Researcher
+ Hannett, NM
- Role:
- Researcher
+ Manz, T
- Role:
- Researcher
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 106169/ZZ14/Z
- Publisher:
- University of Oxford
- Publication date:
- 2018
- Version number:
- 3
- Language:
-
English
- Keywords:
- Subjects:
- Pubs id:
-
1480033
- UUID:
-
uuid:c32f1fc0-241b-4af7-813f-f5fb26c7d23c
- Local pid:
-
pubs:1480033
- Deposit date:
-
2018-05-08
Terms of use
- Copyright date:
- 2018
- Notes:
- This document represents version 3 of the TEP datasheet and includes all updates on the project as of April 2018. For more information about TEPs and the TEP Programme, please visit https://thesgc.org/tep.
If you are the owner of this record, you can report an update to it here: Report update to this record