2EU9
Crystal Structure of CLK3
Summary for 2EU9
| Entry DOI | 10.2210/pdb2eu9/pdb |
| Descriptor | Dual specificity protein kinase CLK3, 1,2-ETHANEDIOL (3 entities in total) |
| Functional Keywords | kinase domain, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Isoform 1: Nucleus. Isoform 2: Nucleus speckle: P49761 |
| Total number of polymer chains | 1 |
| Total formula weight | 41854.90 |
| Authors | Papagrigoriou, E.,Rellos, P.,Das, S.,Ugochukwu, E.,Turnbull, A.,von Delft, F.,Bunkoczi, G.,Sobott, F.,Bullock, A.,Fedorov, O.,Gileadi, C.,Savitsky, P.,Edwards, A.,Aerrowsmith, C.,Weigelt, J.,Sundstrom, M.,Knapp, S. (deposition date: 2005-10-28, release date: 2005-11-08, Last modification date: 2024-02-14) |
| Primary citation | 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 Cited by 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: 19278650DOI: 10.1016/j.str.2008.12.023 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.53 Å) |
Structure validation
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