3E1Z

Crystal structure of the parasite protesase inhibitor chagasin in complex with papain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.166 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteases.

Redzynia, I.Ljunggren, A.Bujacz, A.Abrahamson, M.Jaskolski, M.Bujacz, G.

(2009) FEBS J 276: 793-806

  • DOI: https://doi.org/10.1111/j.1742-4658.2008.06824.x
  • Primary Citation of Related Structures:  
    3E1Z

  • PubMed Abstract: 

    A complex of chagasin, a protein inhibitor from Trypanosoma cruzi, and papain, a classic family C1 cysteine protease, has been crystallized. Kinetic studies revealed that inactivation of papain by chagasin is very fast (k(on) = 1.5 x 10(6) M(-1) x s(-1)), and results in the formation of a very tight, reversible complex (K(i) = 36 pM), with similar or better rate and equilibrium constants than those for cathepsins L and B. The high-resolution crystal structure shows an inhibitory wedge comprising three loops, which forms a number of contacts responsible for the high-affinity binding. Comparison with the structure of papain in complex with human cystatin B reveals that, despite entirely different folding, the two inhibitors utilize very similar atomic interactions, leading to essentially identical affinities for the enzyme. Comparisons of the chagasin-papain complex with high-resolution structures of chagasin in complexes with cathepsin L, cathepsin B and falcipain allowed the creation of a consensus map of the structural features that are important for efficient inhibition of papain-like enzymes. The comparisons also revealed a number of unique interactions that can be used to design enzyme-specific inhibitors. As papain exhibits high structural similarity to the catalytic domain of the T. cruzi enzyme cruzipain, the present chagasin-papain complex provides a reliable model of chagasin-cruzipain interactions. Such information, coupled with our identification of specificity-conferring interactions, should be important for the development of drugs for treatment of the devastating Chagas disease caused by this parasite.


  • Organizational Affiliation

    Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Technical University of Lodz, Poland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
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
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Papain212Carica papayaMutation(s): 0 
EC: 3.4.22.2
UniProt
Find proteins for P00784 (Carica papaya)
Explore P00784 
Go to UniProtKB:  P00784
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00784
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
G [auth B]ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
FMT
Query on FMT

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
H [auth B]
I [auth B]
D [auth A],
E [auth A],
F [auth A],
H [auth B],
I [auth B],
J [auth B],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.166 
  • Space Group: I 4 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.13α = 90
b = 99.13β = 90
c = 159.49γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-01-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description