› 4c0c

X-ray diffraction
2.04Å 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)-4-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-fluorobenzamide.

Released:
DOI: 10.2210/pdb4c0c/pdb
PDB entry 4c0c coloured by chain, front view.
PDB entry 4c0c coloured by chain, side view.
PDB entry 4c0c coloured by chain, top view.
Source organism: Trypanosoma cruzi
Primary publication:
4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.
Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust LM
J Med Chem 57 6989-7005 (2014)
PMID: 25101801

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:
homo trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-182236 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Sterol 14-alpha demethylase Chain: A
Molecule details ›
Chain: A
Length: 467 amino acids
Theoretical weight: 53.29 KDa
Source organism: Trypanosoma cruzi
Expression system: Escherichia coli K-12
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

4 bound ligands:
Ligand HEM 1 x HEM
Ligand WVH 1 x WVH
Ligand SO4 13 x SO4
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 8.3.1
Spacegroup: P6322
Unit cell:
a: 128.528Å b: 128.528Å c: 116.721Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.202 0.199 0.254
Expression system: Escherichia coli K-12

Quick links

Citations

5 review citations

Chagas disease research and development: Is there light at the end of the tunnel?
Chatelain E. (2017)
4 more

3 mentions without citation

4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.
Calvet et al. (2014)
2 more