2EU9

Crystal Structure of CLK3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.53 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.

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.

(2009) Structure 17: 352-362

  • DOI: https://doi.org/10.1016/j.str.2008.12.023
  • Primary Citation of Related Structures:  
    1Z57, 2EU9

  • 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.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Oxford, Old Road Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dual specificity protein kinase CLK3355Homo sapiensMutation(s): 0 
Gene Names: CLK3
EC: 2.7.12.1
UniProt & NIH Common Fund Data Resources
Find proteins for P49761 (Homo sapiens)
Explore P49761 
Go to UniProtKB:  P49761
PHAROS:  P49761
GTEx:  ENSG00000179335 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49761
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
B [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.53 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.171 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 108.727α = 90
b = 45.063β = 115.23
c = 84.006γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-08
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-05-02
    Changes: Structure summary
  • Version 1.4: 2012-08-29
    Changes: Database references
  • Version 1.5: 2024-02-14
    Changes: Data collection, Database references, Derived calculations