Published June 17, 2016
| Version 9
Dataset
Open
Human Cyclin-dependent kinase 12 (CDK12), kinase domain; A Target Enabling Package
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
- Gregg B. Morin
- Nathanael S. Gray
- 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 document represents version 9 of the TEP datasheet and includes all updates on the project as of March 2021. For more information about TEPs and the TEP Programme, please visit https://thesgc.org/tep.
Files
CDK12_TEP_v9.pdf
Files
(1.3 MB)
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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