2OUL

The Structure of Chagasin in Complex with a Cysteine Protease Clarifies the Binding Mode and Evolution of a New Inhibitor Family


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family.

Wang, S.X.Pandey, K.C.Scharfstein, J.Whisstock, J.Huang, R.K.Jacobelli, J.Fletterick, R.J.Rosenthal, P.J.Abrahamson, M.Brinen, L.S.Rossi, A.Sali, A.McKerrow, J.H.

(2007) Structure 15: 535-543

  • DOI: https://doi.org/10.1016/j.str.2007.03.012
  • Primary Citation of Related Structures:  
    2OUL

  • PubMed Abstract: 

    Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds.


  • Organizational Affiliation

    Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Falcipain 2241Plasmodium falciparum 3D7Mutation(s): 0 
Gene Names: AAF97809
EC: 3.4.22
UniProt
Find proteins for Q8I6U4 (Plasmodium falciparum (isolate 3D7))
Explore Q8I6U4 
Go to UniProtKB:  Q8I6U4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8I6U4
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Chagasin110Trypanosoma cruziMutation(s): 0 
Gene Names: cha
UniProt
Find proteins for Q966X9 (Trypanosoma cruzi)
Explore Q966X9 
Go to UniProtKB:  Q966X9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ966X9
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.189 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.236α = 90
b = 94.236β = 90
c = 119.764γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing
ADSCdata collection

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-02-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Source and taxonomy, Version format compliance
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Refinement description