4NST

Crystal structure of human Cdk12/Cyclin K in complex with ADP-aluminum fluoride

4NST の概要

• エントリーDOI: 10.2210/pdb4nst/pdb
• 分子名称: Cyclin-dependent kinase 12, Cyclin-K, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: transcription, rna polymerase ii, phosphorylation, transferase-transcription complex, transferase/transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q9NYV4 O75909
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 145829.09

構造登録者

Boesken, C.A.,Farnung, L.,Anand, K.,Geyer, M. (登録日: 2013-11-29, 公開日: 2014-03-26, 最終更新日: 2024-10-16)

主引用文献

Bosken, C.A.,Farnung, L.,Hintermair, C.,Merzel Schachter, M.,Vogel-Bachmayr, K.,Blazek, D.,Anand, K.,Fisher, R.P.,Eick, D.,Geyer, M.
The structure and substrate specificity of human Cdk12/Cyclin K.
Nat Commun, 5:3505-3505, 2014

PubMed Abstract: Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases.

PubMed: 24662513
DOI: 10.1038/ncomms4505

実験手法

X-RAY DIFFRACTION (2.2 Å)