1ZIV

Catalytic Domain of Human Calpain-9


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The crystal structures of human calpains 1 and 9 imply diverse mechanisms of action and auto-inhibition.

Davis, T.L.Walker, J.R.Finerty, P.J.Mackenzie, F.Newman, E.M.Dhe-Paganon, S.

(2007) J Mol Biol 366: 216-229

  • DOI: https://doi.org/10.1016/j.jmb.2006.11.037
  • Primary Citation of Related Structures:  
    1ZIV, 2ARY

  • PubMed Abstract: 

    Calpains are calcium activated cysteine proteases found throughout the animal, plant, and fungi kingdoms; 14 isoforms have been described in the human genome. Calpains have been implicated in multiple models of human disease; for instance, calpain 1 is activated in the brains of individuals with Alzheimer's disease, and the digestive tract specific calpain 9 is down-regulated in gastric cancer cell lines. We have solved the structures of human calpain 1 and calpain 9 protease cores using crystallographic methods; both structures have clear implications for the function of non-catalytic domains of full-length calpains in the calcium-mediated activation of the enzyme. The structure of minicalpain 1 is similar to previously solved structures of the protease core. Auto-inhibition in this system is most likely through rearrangements of a central helical/loop region near the active site cysteine, which occlude the substrate binding site. However, the structure of minicalpain 9 indicates that auto-inhibition in this enzyme is mediated through large intra-domain movements that misalign the catalytic triad. This disruption is reminiscent of the full-length inactive calpain conformation. The structures of the highly conserved, ubiquitously expressed human calpain 1 and the more tissue specific human calpain 9 indicate that although there are high levels of sequence conservation throughout the calpain family, isolated structures of family members are insufficient to explain the molecular mechanism of activation for this group of proteins.


  • Organizational Affiliation

    Structural Genomics Consortium and the Department of Physiology, University of Toronto, 100 College Street, Toronto, Ontario, Canada M5G 1L5.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calpain 9339Homo sapiensMutation(s): 0 
Gene Names: CAPN9NCL4
EC: 3.4.22
UniProt & NIH Common Fund Data Resources
Find proteins for O14815 (Homo sapiens)
Explore O14815 
Go to UniProtKB:  O14815
PHAROS:  O14815
GTEx:  ENSG00000135773 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14815
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.207 
  • Space Group: P 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.308α = 90
b = 80.9β = 90
c = 100.545γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-07-05
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description