1Z57

Crystal structure of human CLK1 in complex with 10Z-Hymenialdisine

1Z57 の概要

• エントリーDOI: 10.2210/pdb1z57/pdb
• 関連するPDBエントリー: 1jow
• 分子名称: Dual specificity protein kinase CLK1, DEBROMOHYMENIALDISINE (3 entities in total)
• 機能のキーワード: protein tyrosine kinase, dual specificity, splicing, human, 10z-hymendialdisine, structural genomics, structural genomics consortium, sgc, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P49759
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39826.75

構造登録者

Debreczeni, J.,Das, S.,Knapp, S.,Bullock, A.,Guo, K.,Amos, A.,Fedorov, O.,Edwards, A.,Sundstrom, M.,von Delft, F.,Niesen, F.H.,Ball, L.,Sobott, F.,Arrowsmith, C.,Structural Genomics Consortium (SGC) (登録日: 2005-03-17, 公開日: 2005-04-12, 最終更新日: 2023-08-23)

主引用文献

Bullock, A.N.,Das, S.,Debreczeni, J.E.,Rellos, P.,Fedorov, O.,Niesen, F.H.,Guo, K.,Papagrigoriou, E.,Amos, A.L.,Cho, S.,Turk, B.E.,Ghosh, G.,Knapp, S.
Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.
Structure, 17:352-362, 2009

PubMed Abstract: Splicing requires reversible phosphorylation of serine/arginine-rich (SR) proteins, which direct splice site selection in eukaryotic mRNA. These phosphorylation events are dependent on SR protein (SRPK) and cdc2-like kinase (CLK) families. SRPK1 phosphorylation of splicing factors is restricted by a specific docking interaction whereas CLK activity is less constrained. To understand functional differences between splicing factor targeting kinases, we determined crystal structures of CLK1 and CLK3. Intriguingly, in CLKs the SRPK1 docking site is blocked by insertion of a previously unseen helix alphaH. In addition, substrate docking grooves present in related mitogen activating protein kinases (MAPKs) are inaccessible due to a CLK specific beta7/8-hairpin insert. Thus, the unconstrained substrate interaction together with the determined active-site mediated substrate specificity allows CLKs to complete the functionally important hyperphosphorylation of splicing factors like ASF/SF2. In addition, despite high sequence conservation, we identified inhibitors with surprising isoform specificity for CLK1 over CLK3.

PubMed: 19278650
DOI: 10.1016/j.str.2008.12.023

実験手法

X-RAY DIFFRACTION (1.7 Å)