1NX3

Calpain Domain VI in Complex with the Inhibitor PD150606


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A structural model for the inhibition of calpain by calpastatin: crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor.

Todd, B.Moore, D.Deivanayagam, C.C.S.Lin, G.-D.Chattopadhyay, D.Maki, M.Wang, K.K.W.Narayana, S.V.L.

(2003) J Mol Biol 328: 131-146

  • DOI: https://doi.org/10.1016/s0022-2836(03)00274-2
  • Primary Citation of Related Structures:  
    1NX0, 1NX1, 1NX2, 1NX3

  • PubMed Abstract: 

    The Ca(2+)-dependent cysteine protease calpain along with its endogenous inhibitor calpastatin is widely distributed. The interactions between calpain and calpastatin have been studied to better understand the nature of calpain inhibition by calpastatin, which can aid the design of small molecule inhibitors to calpain. Here we present the crystal structure of a complex between a calpastatin peptide and the calcium-binding domain VI of calpain. DIC19 is a 19 residue peptide, which corresponds to one of the three interacting domains of calpastatin, which is known to interact with domain VI of calpain. We present two crystal structures of DIC19 bound to domain VI of calpain, determined by molecular replacement methods to 2.5A and 2.2A resolution. In the process of crystallizing the inhibitor complex, a new native crystal form was identified which had the homodimer 2-fold axis along a crystallographic axis as opposed to the previously observed dimer in the asymmetric unit. The crystal structures of the native domain VI and its inhibitor PD150606 (3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid) complex were determined with the help of molecular replacement methods to 2.0A and 2.3A resolution, respectively. In addition, we built a homology model for the complex between domain IV and DIA19 peptide of calpastatin. Finally, we present a model for the calpastatin-inhibited calpain.


  • Organizational Affiliation

    Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calcium-dependent protease, small subunit173Sus scrofaMutation(s): 0 
Gene Names: CAPNS1 OR CAPN4
UniProt
Find proteins for P04574 (Sus scrofa)
Explore P04574 
Go to UniProtKB:  P04574
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04574
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.210 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.578α = 90
b = 78.578β = 90
c = 77.891γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-08-19
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2012-05-02
    Changes: Structure summary
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations