› 3h4v

X-ray diffraction
2.4Å resolution

Selective screening and design to identify inhibitors of leishmania major pteridine reductase 1

Released:
DOI: 10.2210/pdb3h4v/pdb
PDB entry 3h4v coloured by chain, front view.
PDB entry 3h4v coloured by chain, side view.
PDB entry 3h4v coloured by chain, top view.
Source organism: Leishmania major
Primary publication:
Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development.
Cavazzuti A, Paglietti G, Hunter WN, Gamarro F, Piras S, Loriga M, Allecca S, Corona P, McLuskey K, Tulloch L, Gibellini F, Ferrari S, Costi MP
Proc Natl Acad Sci U S A 105 1448-53 (2008)
PMID: 18245389

Function and Biology Details

Reaction catalysed: 
5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = biopterin + 2 NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-169629 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Pteridine reductase 1 Chains: A, B, C, D, E, F, G, H
Molecule details ›
Chains: A, B, C, D, E, F, G, H
Length: 288 amino acids
Theoretical weight: 30.44 KDa
Source organism: Leishmania major
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: Q01782 (Residues: 1-288; Coverage: 100%)
Gene names: HMTXR, L1063.01, LmjF23.0270, LmjF_23_0270, PTR1
Sequence domains: Enoyl-(Acyl carrier protein) reductase
Structure domains: NAD(P)-binding Rossmann-like Domain

Ligands and Environments


Cofactor: Ligand NAP 8 x NAP
1 bound ligand:
Ligand DVP 8 x DVP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-4
Spacegroup: P21
Unit cell:
a: 95.206Å b: 103.492Å c: 146.476Å
α: 90° β: 108.24° γ: 90°
R-values:
R R work R free
0.28 0.276 0.356
Expression system: Escherichia coli BL21

Quick links

Citations

10 review citations

Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.
Nagle et al. (2014)
9 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