› 4by0

X-ray diffraction
3.1Å resolution

Crystal structure of Trypanosoma cruzi CYP51 bound to the inhibitor (R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-3,3'- difluoro-(1,1'-biphenyl)-4-carboxamide

Released:
DOI: 10.2210/pdb4by0/pdb
PDB entry 4by0 coloured by chain, front view.
PDB entry 4by0 coloured by chain, side view.
PDB entry 4by0 coloured by chain, top view.
Source organism: Trypanosoma cruzi
Primary publication:
R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi.
Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR
ACS Med Chem Lett 5 434-9 (2014)
PMID: 24900854

Function and Biology Details

Reaction catalysed: 
(1a) a 14-alpha-methylsteroid + [reduced NADPH--hemoprotein reductase] + O(2) = a 14-alpha-hydroxysteroid + [oxidized NADPH--hemoprotein reductase] + H(2)O
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-182234 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Sterol 14-alpha demethylase Chains: A, B
Molecule details ›
Chains: A, B
Length: 467 amino acids
Theoretical weight: 53.29 KDa
Source organism: Trypanosoma cruzi
Expression system: Escherichia coli
UniProt:
  • Canonical: Q7Z1V1 (Residues: 32-481; Coverage: 94%)
Gene names: CYP51, Tc00.1047053506297.260, Tc00.1047053510101.50
Sequence domains: Cytochrome P450
Structure domains: Cytochrome P450

Ligands and Environments

2 bound ligands:
Ligand HEM 2 x HEM
Ligand 5PS 2 x 5PS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 8.3.1
Spacegroup: P3221
Unit cell:
a: 124.167Å b: 124.167Å c: 119.839Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.235 0.232 0.297
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Drug strategies targeting CYP51 in neglected tropical diseases.
Choi et al. (2014)
1 more

3 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)
2 more