› 4bmm

X-ray diffraction
2.84Å 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)-2',3, 5'-trifluoro-(1,1'-biphenyl)-4-carboxamide

Released:
DOI: 10.2210/pdb4bmm/pdb
PDB entry 4bmm coloured by chain, front view.
PDB entry 4bmm coloured by chain, side view.
PDB entry 4bmm coloured by chain, top view.
Source organism: Trypanosoma cruzi strain CL Brener
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 dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-182235 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Sterol 14-alpha demethylase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 467 amino acids
Theoretical weight: 53.29 KDa
Source organism: Trypanosoma cruzi strain CL Brener
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

2 bound ligands:
Ligand HEM 4 x HEM
Ligand TU1 4 x TU1
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 8.3.1
Spacegroup: C2
Unit cell:
a: 272.469Å b: 66.452Å c: 122.219Å
α: 90° β: 110.65° γ: 90°
R-values:
R R work R free
0.194 0.189 0.29
Expression system: Escherichia coli K-12

Quick links

Citations

4 review citations

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

2 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)
1 more