Published June 17, 2016
| Version 2
Dataset
Open
Human Cyclin-dependent kinase 12 (CDK12), kinase domain; A Target Enabling Package
Authors/Creators
- Sarah E. Dixon-Clarke
- Jonathan M. Elkins
- S.-W. Grace Cheng
- Tinghu Zhang
- Nicholas Kwiatkowski
- Calla M. Olson
- Brian J. Abraham
- Ann K. Greifenberg
- Scott B. Ficarro
- Yanke Liang
- Nancy M. Hannett
- Theresa Manz
- Mingfeng Hao
- Bartlomiej Bartkowiak
- Arno L. Greenleaf
- Jarrod A. Marto
- Matthias Geyer
- Richard A. Young
- Nathanael S. Gray
- Gregg B. Morin
- Alex N. Bullock
Description
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.
Notes
This deposition represents version 2 of the TEP datasheet. Changes include, but are not limited to: Addition of hyperlinks throughout the body of the datasheet; Addition of Useful Links to relevant databases; Addition of a Reference box where applicable; Other modifications necessary for page spacing and visualisation. Please note, all data and results within the document remain the same as provided in version 1.
To see version 1: https://doi.org/10.5287/bodleian:zgNjZeGBE
Files
CDK12_TEP_datasheet_v2.pdf
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Additional details
Related works
- Is part of
- https://www.thesgc.org/tep (URL)
Funding
- Wellcome Trust
- A UK Hub to Catalyse Open Target Discovery. 106169