4CK8: Sterol 14-alpha Demethylase (cyp51)from Trypanosoma Cruzi In Complex With (r)-1-(2,4-dichlorophenyl)-2-(1h-imidazol-1-yl)ethyl 4-(4-(3,4-dichlorophenyl)piperazin-1-yl)phenylcarbamate (lfd)

Citation:
Abstract
Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14alpha-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of beta-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50 = 1.2 nM, vs (S)-2/(S)-3, EC50 = 1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.
PDB ID: 4CK8Download
MMDB ID: 121864
PDB Deposition Date: 2013/12/30
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 2.62  Å
Source Organism:
Similar Structures:
Biological Unit for 4CK8: monomeric; determined by author and by software (PISA)
Molecular Components in 4CK8
Label Count Molecule
Protein (1 molecule)
1
Sterol 14-alpha Demethylase(Gene symbol: Tc00.1047053506297.260)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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