3C0G

CASK CaM-Kinase Domain- 3'-AMP complex, P1 form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

CASK Functions as a Mg2+-independent neurexin kinase

Mukherjee, K.Sharma, M.Urlaub, H.Bourenkov, G.P.Jahn, R.Sudhof, T.C.Wahl, M.C.

(2008) Cell 133: 328-339

  • DOI: https://doi.org/10.1016/j.cell.2008.02.036
  • Primary Citation of Related Structures:  
    3C0G, 3C0H, 3C0I

  • PubMed Abstract: 

    CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical MAGUK domains. The CASK CaM-kinase domain is presumed to be a catalytically inactive pseudokinase because it lacks the canonical DFG motif required for Mg2+ binding that is thought to be indispensable for kinase activity. Here we show, however, that CASK functions as an active protein kinase even without Mg2+ binding. High-resolution crystal structures reveal that the CASK CaM-kinase domain adopts a constitutively active conformation that binds ATP and catalyzes phosphotransfer without Mg2+. The CASK CaM-kinase domain phosphorylates itself and at least one physiological interactor, the synaptic protein neurexin-1, to which CASK is recruited via its PDZ domain. Thus, our data indicate that CASK combines the scaffolding activity of MAGUKs with an unusual kinase activity that phosphorylates substrates recuited by the scaffolding activity. Moreover, our study suggests that other pseudokinases (10% of the kinome) could also be catalytically active.


  • Organizational Affiliation

    Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9111, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peripheral plasma membrane protein CASK
A, B
351Homo sapiensMutation(s): 0 
Gene Names: CASK
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O14936 (Homo sapiens)
Explore O14936 
Go to UniProtKB:  O14936
PHAROS:  O14936
GTEx:  ENSG00000147044 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14936
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3AM
Query on 3AM

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate
C10 H14 N5 O7 P
LNQVTSROQXJCDD-KQYNXXCUSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.328α = 90
b = 60.267β = 106.49
c = 60.553γ = 105.8
Software Package:
Software NamePurpose
REFMACrefinement
MAR345dtbdata collection
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-04-29 
  • Deposition Author(s): Wahl, M.C.

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2024-03-13
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2024-04-03
    Changes: Refinement description