2VZ6

Structure of human calcium calmodulin dependent protein kinase type II alpha (CAMK2A) in complex with Indirubin E804


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure of the Camkiidelta/Calmodulin Complex Reveals the Molecular Mechanism of Camkii Kinase Activation.

Rellos, P.Pike, A.C.W.Niesen, F.H.Salah, E.Lee, W.H.von Delft, F.Knapp, S.

(2010) PLoS Biol 8: 426

  • DOI: https://doi.org/10.1371/journal.pbio.1000426
  • Primary Citation of Related Structures:  
    2UX0, 2V7O, 2VN9, 2VZ6, 2W2C, 2WEL

  • PubMed Abstract: 

    Long-term potentiation (LTP), a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM)-dependent kinase II (CaMKII). CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.


  • Organizational Affiliation

    University of Oxford, Nuffield Department of Clinical Medicine, Structural Genomics Consortium, Oxford, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE TYPE II ALPHA CHAIN
A, B
313Homo sapiensMutation(s): 0 
EC: 2.7.11.17
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UQM7 (Homo sapiens)
Explore Q9UQM7 
Go to UniProtKB:  Q9UQM7
PHAROS:  Q9UQM7
GTEx:  ENSG00000070808 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UQM7
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.244α = 90
b = 113.621β = 90
c = 131.868γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2011-08-10
    Changes: Database references, Derived calculations
  • Version 1.3: 2018-01-24
    Changes: Database references
  • Version 1.4: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description