› 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 4by0 coloured by chain and viewed from the front.
PDB 4by0 coloured by chain and viewed from the side.
PDB 4by0 coloured by chain and viewed from the top.
Source organism: Trypanosoma cruzi
Entry authors: Choi JY, Calvet CM, Vierira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR

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)
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

3 review citations

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis.
Pacheco et al. (2022)
2 more

2 mentions without citation

Expanding the binding envelope of CYP51 inhibitors targeting Trypanosoma cruzi with 4-aminopyridyl-based sulfonamide derivatives.
Vieira et al. (2014)
1 more