2LL7

Solution NMR structure of CaM bound to the eNOS CaM binding domain peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure and Dynamics of Calmodulin (CaM) Bound to Nitric Oxide Synthase Peptides: Effects of a Phosphomimetic CaM Mutation.

Piazza, M.Futrega, K.Spratt, D.E.Dieckmann, T.Guillemette, J.G.

(2012) Biochemistry 51: 3651-3661

  • DOI: https://doi.org/10.1021/bi300327z
  • Primary Citation of Related Structures:  
    2LL6, 2LL7

  • PubMed Abstract: 

    Nitric oxide synthase (NOS) plays a major role in a number of key physiological and pathological processes. Knowledge of how this is regulated is important. The small acidic calcium binding protein, calmodulin (CaM), is required to fully activate the enzyme. The exact mechanism of how CaM activates NOS is not fully understood. Studies have shown CaM to act like a switch that causes a conformational change in NOS to allow for the transfer of an electron between the reductase and oxygenase domains through a process that is thought to be highly dynamic. To investigate the dynamic properties of CaM-NOS interactions, we determined the solution structure of CaM bound to the inducible NOS (iNOS) and endothelial NOS (eNOS) CaM binding region peptides. In addition, we investigated the effect of CaM phosphorylation. Tyrosine 99 (Y99) of CaM is reported to be phosphorylated in vivo. We have produced a phosphomimetic Y99E CaM to investigate the structural and functional effects that the phosphorylation of this residue may have on nitric oxide production. All three mammalian NOS isoforms were included in the investigation. Our results show that a phosphomimetic Y99E CaM significantly reduces the maximal synthase activity of eNOS by 40% while having little effect on nNOS or iNOS activity. A comparative nuclear magnetic resonance study between phosphomimetic Y99E CaM and wild-type CaM bound to the eNOS CaM binding region peptide was performed. This investigation provides important insights into how the increased electronegativity of a phosphorylated CaM protein affects the binding, dynamics, and activation of the NOS enzymes.


  • Organizational Affiliation

    Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calmodulin148Homo sapiensMutation(s): 0 
Gene Names: 
CALM1CALMCAMCAM1CALM2CAM2CAMBCALM3CALML2CAM3...
CALM1CALMCAMCAM1CALM2CAM2CAMBCALM3CALML2CAM3CAMCCAMIII

UniProt & NIH Common Fund Data Resources
Find proteins for P0DP23 (Homo sapiens)
Explore P0DP23 
Go to UniProtKB:  P0DP23
PHAROS:  P0DP23
GTEx:  ENSG00000198668 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DP23
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Nitric oxide synthase, endothelial17Homo sapiensMutation(s): 0 
Gene Names: NOS3
EC: 1.14.13.39
UniProt & NIH Common Fund Data Resources
Find proteins for P29474 (Homo sapiens)
Explore P29474 
Go to UniProtKB:  P29474
PHAROS:  P29474
GTEx:  ENSG00000164867 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29474
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-16
    Type: Initial release
  • Version 1.1: 2023-06-14
    Changes: Database references, Other
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references