1NDA

THE STRUCTURE OF TRYPANOSOMA CRUZI TRYPANOTHIONE REDUCTASE IN THE OXIDIZED AND NADPH REDUCED STATE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

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This is version 1.3 of the entry. See complete history


Literature

The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state.

Lantwin, C.B.Schlichting, I.Kabsch, W.Pai, E.F.Krauth-Siegel, R.L.

(1994) Proteins 18: 161-173

  • DOI: https://doi.org/10.1002/prot.340180208
  • Primary Citation of Related Structures:  
    1NDA

  • PubMed Abstract: 

    The three-dimensional structure of trypanothione reductase (TR) (EC 1.6.4.8) from Trypanosoma cruzi has been solved at 0.33 nm resolution by molecular replacement using the structure of C. fasciculata TR as a starting model. Elucidation of the T. cruzi TR structure represents the first step in the rational design of a drug against Chagas' disease. The structure of T. cruzi TR is compared with those of C. fasciculata TR as well as human and E. coli glutathione reductase (GR). In the FAD-binding domain, TR has two insertions, each about 10 residues long, which do not occur in GR. The first one is a rigid loop stabilizing the position of helix 91-117 which is responsible for the wider active site of TR as compared to GR. The second insertion does not occur where it is predicted by sequence alignment; rather the residues extend three strands of the 4-stranded beta-sheet by one or two residues each. This increases the number of hydrogen bonds within the sheet structure. The structure of the NADPH.TR complex has been solved at 0.33 nm resolution. The nicotinamide ring is sandwiched between the flavin ring and the side chain of Phe-198 which undergoes the same conformational change upon coenzyme binding as Tyr-197 in GR. In addition to Arg-222 and Arg-228, which are conserved in TR and GR, Tyr-221--the last residue of the second beta-sheet strand of the beta alpha beta dinucleotide binding fold--is in hydrogen bonding distance to the 2' phosphate group of NADPH.


  • Organizational Affiliation

    Abteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Heidelberg, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRYPANOTHIONE OXIDOREDUCTASE
A, B, C, D
491Trypanosoma cruziMutation(s): 0 
UniProt
Find proteins for P28593 (Trypanosoma cruzi)
Explore P28593 
Go to UniProtKB:  P28593
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28593
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 136.3α = 90
b = 91.1β = 94
c = 126γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-09-30
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-11-29
    Changes: Derived calculations, Other