1TL9

High resolution crystal structure of calpain I protease core in complex with leupeptin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal Structures of Calpain-E64 and -Leupeptin Inhibitor Complexes Reveal Mobile Loops Gating the Active Site

Moldoveanu, T.Campbell, R.L.Cuerrier, D.Davies, P.L.

(2004) J Mol Biol 343: 1313-1326

  • DOI: https://doi.org/10.1016/j.jmb.2004.09.016
  • Primary Citation of Related Structures:  
    1TL9, 1TLO

  • PubMed Abstract: 

    The endogenous calpain inhibitor, calpastatin, modulates some patho-physiological aspects of calpain signaling. Excess calpain can escape this inhibition and as well, many calpain isoforms and autolytically generated protease core fragments are not inhibited by calpastatin. There is a need, therefore, to develop specific, cell-permeable calpain inhibitors to block uncontrolled proteolysis and prevent tissue damage during brain and heart ischemia, spinal-cord injury and Alzheimer's diseases. Here, we report the first high-resolution crystal structures of rat mu-calpain protease core complexed with two traditional, low molecular mass inhibitors, leupeptin and E64. These structures show that access to a slightly deeper, but otherwise papain-like active site is gated by two flexible loops. These loops are divergent among the calpain isoforms giving a potential structural basis for substrate/inhibitor selectivity over other papain-like cysteine proteases and between members of the calpain family.


  • Organizational Affiliation

    Department of Biochemistry, Queen's University, Kingston, Ont. K7L 3N6, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calpain 1, large [catalytic] subunit339Rattus norvegicusMutation(s): 0 
Gene Names: CAPN1CLS1
EC: 3.4.22.52
UniProt
Find proteins for P97571 (Rattus norvegicus)
Explore P97571 
Go to UniProtKB:  P97571
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97571
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
leupeptin inhibitor4Streptomyces roseusMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
AR7
Query on AR7
B
PEPTIDE-LIKEC6 H17 N4 O2ARG
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.67α = 90
b = 68.16β = 90
c = 91.14γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
XFITdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-02
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other