› 3tik

X-ray diffraction
2.05Å resolution

Sterol 14-alpha demethylase (CYP51) from Trypanosoma brucei in complex with the tipifarnib derivative 6-((4-chlorophenyl)(methoxy)(1-methyl-1H-imidazol-5-yl)methyl)-4-(2,6-difluorophenyl)-1-methylquinolin-2(1H)-one

Released:
DOI: 10.2210/pdb3tik/pdb
PDB entry 3tik coloured by chain, front view.
PDB entry 3tik coloured by chain, side view.
PDB entry 3tik coloured by chain, top view.
Source organism: Trypanosoma brucei
Primary publication:
Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib.
Buckner FS, Bahia MT, Suryadevara PK, White KL, Shackleford DM, Chennamaneni NK, Hulverson MA, Laydbak JU, Chatelain E, Scandale I, Verlinde CL, Charman SA, Lepesheva GI, Gelb MH
Antimicrob Agents Chemother 56 4914-21 (2012)
PMID: 22777048

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assemblies composition:
homo tetramer
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-174343 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Lanosterol 14-alpha-demethylase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 454 amino acids
Theoretical weight: 51.3 KDa
Source organism: Trypanosoma brucei
Expression system: Escherichia coli
UniProt:
  • Canonical: Q385E8 (Residues: 32-481; Coverage: 94%)
Gene name: Tb11.02.4080
Sequence domains: Cytochrome P450
Structure domains: Cytochrome P450

Ligands and Environments


Cofactor: Ligand HEM 4 x HEM
1 bound ligand:
Ligand JKF 4 x JKF
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: P1
Unit cell:
a: 59.722Å b: 79.715Å c: 117.521Å
α: 74.47° β: 81.58° γ: 68.05°
R-values:
R R work R free
0.189 0.186 0.243
Expression system: Escherichia coli

Quick links

Citations

8 review citations

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

10 mentions without citation

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