› 3jq9

X-ray diffraction
2.3Å resolution

Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (AX1)

Released:
DOI: 10.2210/pdb3jq9/pdb
PDB entry 3jq9 coloured by chain, front view.
PDB entry 3jq9 coloured by chain, side view.
PDB entry 3jq9 coloured by chain, top view.
Source organism: Trypanosoma brucei
Primary publication:
Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases.
Tulloch LB, Martini VP, Iulek J, Huggan JK, Lee JH, Gibson CL, Smith TK, Suckling CJ, Hunter WN
J Med Chem 53 221-9 (2010)
PMID: 19916554

Function and Biology Details

Reaction catalysed: 
5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = biopterin + 2 NADPH
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-176581 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Pteridine reductase, putative Chains: A, B
Molecule details ›
Chains: A, B
Length: 288 amino acids
Theoretical weight: 30.67 KDa
Source organism: Trypanosoma brucei
Expression system: Escherichia coli
UniProt:
  • Canonical: Q581W1 (Residues: 102-369; Coverage: 73%)
Gene names: Tb08.26N11.790, Tb927.8.2210
Sequence domains: Enoyl-(Acyl carrier protein) reductase
Structure domains: NAD(P)-binding Rossmann-like Domain
Pteridine reductase, putative Chains: C, D
Molecule details ›
Chains: C, D
Length: 288 amino acids
Theoretical weight: 30.69 KDa
Source organism: Trypanosoma brucei
Expression system: Escherichia coli
UniProt:
  • Canonical: Q581W1 (Residues: 102-369; Coverage: 73%)
Gene names: Tb08.26N11.790, Tb927.8.2210
Sequence domains: Enoyl-(Acyl carrier protein) reductase
Structure domains: NAD(P)-binding Rossmann-like Domain

Ligands and Environments


Cofactor: Ligand NAP 4 x NAP
1 bound ligand:
Ligand AX1 4 x AX1
1 modified residue:
Ligand CSX 2 x CSX

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P21
Unit cell:
a: 74.253Å b: 89.201Å c: 84.569Å
α: 90° β: 115.69° γ: 90°
R-values:
R R work R free
0.233 0.231 0.286
Expression system: Escherichia coli

Quick links

Citations

5 review citations

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases.
Kourbeli et al. (2021)
4 more

4 mentions without citation

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.
Ogungbe et al. (2016)
3 more