› 6btl

X-ray diffraction
2.8Å resolution

Crystal structure of Trypanothione Reductase from Trypanosoma brucei in complex with inhibitor RD117 1-[2-(Piperazin-1-yl)ethyl]-5-{5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl}-1H-indole

Released:
DOI: 10.2210/pdb6btl/pdb
PDB entry 6btl coloured by chain, front view.
PDB entry 6btl coloured by chain, side view.
PDB entry 6btl coloured by chain, top view.
Source organism: Trypanosoma brucei brucei TREU927
Primary publication:
Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma.
De Gasparo R, Brodbeck-Persch E, Bryson S, Hentzen NB, Kaiser M, Pai EF, Krauth-Siegel RL, Diederich F
ChemMedChem 13 957-967 (2018)
PMID: 29624890

Function and Biology Details

Reaction catalysed: 
Trypanothione + NADP(+) = trypanothione disulfide + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-174386 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Trypanothione reductase Chains: A, B
Molecule details ›
Chains: A, B
Length: 495 amino acids
Theoretical weight: 53.5 KDa
Source organism: Trypanosoma brucei brucei TREU927
Expression system: Escherichia coli
UniProt:
  • Canonical: Q389T8 (Residues: 1-492; Coverage: 100%)
Gene name: Tb10.406.0520
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand FAD 2 x FAD
4 bound ligands:
Ligand SO4 5 x SO4
Ligand RD7 2 x RD7
Ligand GOL 4 x GOL
Ligand EPE 2 x EPE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 23-ID-D
Spacegroup: P43212
Unit cell:
a: 117.664Å b: 117.664Å c: 225.163Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.198 0.196 0.236
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases.
Battista et al. (2020)
1 more

1 mention without citation

Polyamines in protozoan pathogens.
Phillips MA. (2018)