› 2wp5

X-ray diffraction
2.8Å resolution

Trypanosoma brucei trypanothione reductase in complex with 3,4- dihydroquinazoline inhibitor (DDD00065414)

Released:
DOI: 10.2210/pdb2wp5/pdb
PDB entry 2wp5 coloured by chain, front view.
PDB entry 2wp5 coloured by chain, side view.
PDB entry 2wp5 coloured by chain, top view.
Source organism: Trypanosoma brucei brucei TREU927
Primary publication:
Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.
Patterson S, Alphey MS, Jones DC, Shanks EJ, Street IP, Frearson JA, Wyatt PG, Gilbert IH, Fairlamb AH
OpenAccess logo J Med Chem 54 6514-30 (2011)
PMID: 21851087

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 dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-174385 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Trypanothione reductase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 495 amino acids
Theoretical weight: 53.5 KDa
Source organism: Trypanosoma brucei brucei TREU927
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q389T8 (Residues: 1-492; Coverage: 100%)
Gene name: Tb10.406.0520
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand FAD 4 x FAD
5 bound ligands:
Ligand WP5 4 x WP5
Ligand CL 8 x CL
Ligand NA 6 x NA
Ligand MRD 2 x MRD
Ligand MPD 2 x MPD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-4
Spacegroup: P21
Unit cell:
a: 100.94Å b: 63.3Å c: 169.41Å
α: 90° β: 98.09° γ: 90°
R-values:
R R work R free
0.167 0.164 0.219
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

12 review citations

Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need.
Field et al. (2017)
11 more

4 mentions without citation

Polyamines in protozoan pathogens.
Phillips MA. (2018)
3 more