3BLR

Crystal Structure of Human CDK9/cyclinT1 in complex with Flavopiridol

3BLR の概要

• エントリーDOI: 10.2210/pdb3blr/pdb
• 関連するPDBエントリー: 3BLH 3BLQ
• 分子名称: Cell division protein kinase 9, Cyclin-T1, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: transcriptional cdk-cyclin complex, phosphorylated, flavopiridol, alternative splicing, atp-binding, kinase, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transcription regulation, transferase, acetylation, cell cycle, cell division, coiled coil, host-virus interaction, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P50750 O60563
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68860.26

構造登録者

Baumli, S.,Lolli, G.,Lowe, E.D.,Johnson, L.N. (登録日: 2007-12-11, 公開日: 2008-07-01, 最終更新日: 2024-10-30)

主引用文献

Baumli, S.,Lolli, G.,Lowe, E.D.,Troiani, S.,Rusconi, L.,Bullock, A.N.,Debreczeni, J.E.,Knapp, S.,Johnson, L.N.
The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation
Embo J., 27:1907-1918, 2008

PubMed Abstract: The positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. To understand the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2. There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested by a relative rotation of 26 degrees of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions. The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. The CycT1 C-terminal helix shows flexibility that may be important for the interaction of this region with HIV TAT and HEXIM. Flavopiridol, an anticancer drug in phase II clinical trials, binds to the ATP site of CDK9 inducing unanticipated structural changes that bury the inhibitor. CDK9 activity and recognition of regulatory proteins are governed by autophosphorylation. We show that CDK9/CycT1 autophosphorylates on Thr186 in the activation segment and three C-terminal phosphorylation sites. Autophosphorylation on all sites occurs in cis.

PubMed: 18566585
DOI: 10.1038/emboj.2008.121

実験手法

X-RAY DIFFRACTION (2.8 Å)