› 3zg3

X-ray diffraction
2.9Å resolution

STEROL 14-ALPHA DEMETHYLASE (CYP51)FROM TRYPANOSOMA CRUZI IN COMPLEX WITH THE PYRIDINE INHIBITOR N-(1-(5-(trifluoromethyl)(pyridin-2-yl)) piperidin-4yl)-N-(4-(trifluoromethyl)phenyl)pyridin-3-amine (EPL- BS967, UDD)

Released:
DOI: 10.2210/pdb3zg3/pdb
PDB entry 3zg3 coloured by chain, front view.
PDB entry 3zg3 coloured by chain, side view.
PDB entry 3zg3 coloured by chain, top view.
Source organism: Trypanosoma cruzi
Primary publication:
Complexes of Trypanosoma cruzi sterol 14α-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: structural basis for pathogen selectivity.
Hargrove TY, Wawrzak Z, Alexander PW, Chaplin JH, Keenan M, Charman SA, Perez CJ, Waterman MR, Chatelain E, Lepesheva GI
J Biol Chem 288 31602-15 (2013)
PMID: 24047900

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 Chain: A
Molecule details ›
Chain: A
Length: 460 amino acids
Theoretical weight: 52.55 KDa
Source organism: Trypanosoma cruzi
Expression system: Escherichia coli
UniProt:
  • Canonical: Q7Z1V1 (Residues: 28-481; 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 1 x HEM
Ligand UDD 1 x UDD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: P3121
Unit cell:
a: 62.849Å b: 62.849Å c: 222.395Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.25 0.248 0.289
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Chagas disease drug discovery: toward a new era.
Chatelain E. (2015)
4 more

6 mentions without citation

CYP51 as drug targets for fungi and protozoan parasites: past, present and future.
Lepesheva et al. (2018)
5 more